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Vittori M, Bove P, Signoretti M, Cipriani C, Gasparoli C, Antonucci M, Carilli M, Maiorino F, Iacovelli V, Petta F, Travaglia S, Panei M, Russo P, Bertolo R. Oral supplementation with probiotics, potassium citrate, and magnesium in reducing crystalluria in stone formers: A phase II study. Urologia 2024; 91:681-686. [PMID: 39206631 DOI: 10.1177/03915603241272146] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Crystalluria is an important indicator of renal stone recurrence. Mechanisms underlying urinary stone formation are still not fully understood and raising interests has been giving to intestinal commensal bacteria for their contribute in maintaining urinary solutes equilibrium. The aim of our phase II study was to examine the administration of potassium citrate, magnesium and probiotics in order to reduce crystalluria. MATERIALS AND METHODS Since May 2021, we enrolled 23 patients candidates for ureterorenolithotripsy for calcium oxalate kidney stones with crystalluria and a normal metabolic profile. The analysis was validated by the Institution's Ethical Committee (no. approval STS CE Lazio 1/N-823). At discharge, patients were provided with daily food supplementation for 20 days of 1 billion Lactobacillus paracasei LPC09, 1 billion Lactobacillus plantarum LP01, 1 billion Bifidobacterium breve BR03, potassium (520 mg), citrate (1400 mg), and magnesium (80 mg). Crystalluria was re-assessed at 1, 3, 6, and 12-months follow-up by polarized light microscopy. RESULTS After one month from the oral supplementation, no patient reported crystalluria; at 3 months, among the 20 participants available for re-evaluation, still no patient reported crystalluria. Instead, crystalluria was reported in three patients (15%) at 6 months, and in five patients (25%) at 12 months follow-up. CONCLUSIONS The oral supplementation with Lactobacillus spp. and Bifidobacterium spp. was found able to reduce the prevalence of crystalluria in a cohort of patients with diagnosis of calcium oxalate kidney stones with crystalluria candidate to ureterorenolithotripsy.
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Affiliation(s)
- Matteo Vittori
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Pierluigi Bove
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
- Department of Urology, Tor Vergata University of Rome, Rome, Italy
| | - Marta Signoretti
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Chiara Cipriani
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Cristiano Gasparoli
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Michele Antonucci
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Marco Carilli
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Francesco Maiorino
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Valerio Iacovelli
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Filomena Petta
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Stefano Travaglia
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Massimo Panei
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
| | - Pierluigi Russo
- Department of Urology, Catholic University of the Sacred Heart, Agostino Gemelli Hospital, Rome, Italy
| | - Riccardo Bertolo
- Department of Urology, San Carlo di Nancy Hospital, GVM Care and Research, Rome, Italy
- Department of Urology, University of Verona, Verona, Italy
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Phuong-Nguyen K, McGee SL, Aston-Mourney K, Mcneill BA, Mahmood MQ, Rivera LR. Yoyo Dieting, Post-Obesity Weight Loss, and Their Relationship with Gut Health. Nutrients 2024; 16:3170. [PMID: 39339770 PMCID: PMC11435324 DOI: 10.3390/nu16183170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2024] [Revised: 09/13/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
Excessive body weight is associated with many chronic metabolic diseases and weight loss, so far, remains the gold standard treatment. However, despite tremendous efforts exploring optimal treatments for obesity, many individuals find losing weight and maintaining a healthy body weight difficult. Weight loss is often not sustainable resulting in weight regain and subsequent efforts to lose weight. This cyclic pattern of weight loss and regain is termed "yoyo dieting" and predisposes individuals to obesity and metabolic comorbidities. How yoyo dieting might worsen obesity complications during the weight recurrence phase remains unclear. In particular, there is limited data on the role of the gut microbiome in yoyo dieting. Gut health distress, especially gut inflammation and microbiome perturbation, is strongly associated with metabolic dysfunction and disturbance of energy homeostasis in obesity. In this review, we summarise current evidence of the crosstalk between the gastrointestinal system and energy balance, and the effects of yoyo dieting on gut inflammation and gut microbiota reshaping. Finally, we focus on the potential effects of post-dieting weight loss in improving gut health and identify current knowledge gaps within the field, including gut-derived peptide hormones and their potential suitability as targets to combat weight regain, and how yoyo dieting and associated changes in the microbiome affect the gut barrier and the enteric nervous system, which largely remain to be determined.
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Affiliation(s)
- Kate Phuong-Nguyen
- Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - Sean L McGee
- Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - Kathryn Aston-Mourney
- Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - Bryony A Mcneill
- Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - Malik Q Mahmood
- School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - Leni R Rivera
- Institute for Mental and Physical Health and Clinical Translation (IMPACT), School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
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Zhu J, Wang H, Aisikaer M, Yisimayili Z, Yang T, Zhou W, Zhao J, Yunusi K, Aximujiang K. L.acidophilus HSCC LA042 and HKL suspension ameliorate DSS-induced ulcerative colitis in mice by improving the intestinal barrier inhibiting the NLRP3 inflammasome and pathogenic bacteria. Heliyon 2024; 10:e33053. [PMID: 39027449 PMCID: PMC11254534 DOI: 10.1016/j.heliyon.2024.e33053] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 06/07/2024] [Accepted: 06/13/2024] [Indexed: 07/20/2024] Open
Abstract
Ulcerative Colitis(UC) is a chronic intestinal inflammation affecting the intestines, yet its underlying causes remain unclear. In recent decades, the global prevalence of UC has been on the rise, leading to an increasing demand for therapeutic drugs with minimal side effects. Huan Kui Le (HKL), a traditional Chinese medicine compound, has demonstrated promising efficacy when combined with Lactobacillus acidophilus (Lac.) for UC intervention. However, the precise therapeutic mechanism of this combination remains unknown. The study focused on understanding the mechanisms of UC by examining the effects of Lac. and HKL (LH) treatment. The outcomes discovered that the disruption of gut microbiota, triggered by the activation of the NLRP3 inflammasome, plays a crucial role in UC development. This disruption exacerbates UC symptoms by causing disturbances in inflammatory cytokines and mucosal permeability. We investigated the dynamic changes following the application of this treatment using 16S rRNA sequencing, HE, WB, IHC, and ELISA. Compared with the UC group, LH treatment reduced colon pathological injury, improved colon length, and decreased IL-1 β serum levels. Furthermore, it restored the expression of TJs and preserved mucosal barrier integrity. LH treatment also mitigated colon injury by attenuating the expression of pyroptosis-related genes and proteins, such as NLRP3 and Caspase-1. Additionally, LH treatment altered the gut microbiota's microecology, characterized by a reduction in pathogenic bacteria abundance like Escherichia-shigella and an increase in beneficial bacteria abundance like Akkermansia and Erysipelatoclostridium. Overall, our findings indicate that LH therapy may be associated with intestinal barrier repair, inflammasome inhibition, and gut microbiota regulation, suggesting its potential as a UC treatment.
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Affiliation(s)
- Jiwei Zhu
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Hanming Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Muaitaer Aisikaer
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | | | - Tongtong Yang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Wenjun Zhou
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Jianfeng Zhao
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
| | - Kurexi Yunusi
- Uygur Medical College, Xinjiang Medical University, Urumqi, 830017, China
| | - Kasimujiang Aximujiang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xinjiang Medical University, Urumqi, China
- Xinjiang Key Laboratory of Molecular Biology for Endemic Disease, Urumqi, Xinjiang, 830017, China
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Ma Y, Yang D, Huang J, Liu K, Liu H, Wu H, Bao C. Probiotics for inflammatory bowel disease: Is there sufficient evidence? Open Life Sci 2024; 19:20220821. [PMID: 38585636 PMCID: PMC10998680 DOI: 10.1515/biol-2022-0821] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2023] [Revised: 11/26/2023] [Accepted: 12/11/2023] [Indexed: 04/09/2024] Open
Abstract
Inflammatory bowel disease (IBD) refers to chronic inflammatory disorders of the gut. Ulcerative colitis (UC) and Crohn's disease (CD) are two subtypes of IBD. Evidence suggests that the intestinal microbiota plays a role in the pathogenesis of IBD, so probiotics have garnered a lot of interest as a potential treatment or prevention for IBD. However, clinical evidence of the efficacy of probiotics is still debatable. We performed a literature review. An advanced search considered clinical studies on probiotic for IBD from inception to 2023 in PubMed, Embase, Cochrane Library, and Web of Science. In the treatment of UC with probiotics, only Escherichia coli Nissle 1917 for maintenance treatment of UC in remission, and Bifidobacterium and VSL#3 for induction of remission in patients with mild to moderately active UC have shown strong evidence. Currently, there are no definitive conclusions regarding the effectiveness of probiotics in CD. The mechanism of probiotic treatment for IBD may be related to reducing oxidative stress, repairing the intestinal barrier, regulating intestinal flora balance, and modulating intestinal immune response. Differences in the benefits of probiotics between CD and UC may be attributable to the different lesion extent and immune-mediated pathophysiology. More robust randomized clinical trials are required to validate the efficacy and safety of diverse probiotic strains in IBD.
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Affiliation(s)
- Yueying Ma
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Shanghai University of Traditional Chinese Medicine, Shanghai201203, China
| | - Dandan Yang
- Hong Kong Baptist University, Hong Kong999077, China
| | - Jin Huang
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Shanghai University of Traditional Chinese Medicine, Shanghai201203, China
| | - Kunli Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Shanghai University of Traditional Chinese Medicine, Shanghai201203, China
| | - Huirong Liu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai200030, China
| | - Huangan Wu
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai200030, China
| | - Chunhui Bao
- Yueyang Hospital of Integrated Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai200437, China
- Key Laboratory of Acupuncture and Immunological Effects, Shanghai University of Traditional Chinese Medicine, Shanghai200030, China
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Singh J, Sharma M, Singh H, Arora P, Utreja P, Kumar S. Formulation, Characterization and In Vitro Evaluation of Mesalamine and Bifidobacterium bifidum Loaded Hydrogel Beads in Capsule System for Colon Targeted Delivery. AAPS PharmSciTech 2024; 25:61. [PMID: 38485901 DOI: 10.1208/s12249-024-02764-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2023] [Accepted: 02/10/2024] [Indexed: 03/19/2024] Open
Abstract
Mesalamine is a first-line drug for the treatment of inflammatory bowel diseases. However, its premature release associated with marketed formulations leads to adverse effects like gastric trouble, vomiting, and diarrhoea. To minimize these side effects, colon-targeted drug delivery is essential. Besides conventional pharmacotherapy, bifidogenic probiotics with anti-inflammatory activity has been reported to elicit a significant impact on the remission of ulcerative colitis. Bifidogenic probiotics being acid-labile necessitate developing a gastro-resistant formulation for enhancing the delivery of viable cells to the colon. The present study was aimed at developing a fixed-dose unit dosage form of mucoadhesive hydrogel beads loaded with mesalamine and Bifidobacterium bifidum further encapsulated in Eudragit® capsules for the targeted drug delivery at colonic pH. The hydrogel beads were prepared by ionotropic gelation, with the effect of single and dual-crosslinking approaches on various formulation characteristics studied. Standard size 00 Eudragit® gastro-resistant capsules were prepared and the dried beads were filled inside the capsule shells. The formulation was then evaluated for various parameters, including physicochemical characterization, in vitro biocompatibility and anti-inflammatory activity. No interaction was observed between the drug and the polymers, as confirmed through FTIR, XRD, and DSC analysis. The mean particle size of the beads was ~ 457-485 µm. The optimized formulation showed a drug entrapment efficiency of 95.4 ± 2.58%. The Eudragit® capsule shells disintegrated in approximately 13 min at pH 7.4. The mucoadhesive hydrogel beads sustained the drug release above 18 h, with 50% of the drug released by the end of 12 h. The optimized formulation demonstrated significant (p < 0.05) gastro-resistance, biocompatibility, sustained drug release, cell viability, and anti-inflammatory activity.
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Affiliation(s)
- Jagtar Singh
- Faculty of Pharmaceutical Sciences, PCTE Group of Institutes, Near Baddowal Cantt, Ferozepur Rd, Ludhiana, Punjab, 142021, India
- Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali, Punjab, 160062, India
| | - Mohit Sharma
- Faculty of Pharmaceutical Sciences, PCTE Group of Institutes, Near Baddowal Cantt, Ferozepur Rd, Ludhiana, Punjab, 142021, India
| | - Harmeet Singh
- Faculty of Pharmaceutical Sciences, PCTE Group of Institutes, Near Baddowal Cantt, Ferozepur Rd, Ludhiana, Punjab, 142021, India
| | - Pinky Arora
- School of Bioengineering and Biosciences, Lovely Professional University, Jalandhar - Delhi, Grand Trunk Rd, Phagwara, Punjab, 144411, India
- Faculty of Medical Lab Sciences, PCTE Group of Institutes, Near Baddowal Cantt, Ferozepur Rd, Ludhiana, Punjab, 142021, India
| | - Puneet Utreja
- Faculty of Pharmaceutical Sciences, PCTE Group of Institutes, Near Baddowal Cantt, Ferozepur Rd, Ludhiana, Punjab, 142021, India
| | - Shubham Kumar
- School of Pharmaceutical Sciences, Lovely Professional University, Jalandhar - Delhi, Grand Trunk Rd, Phagwara, Punjab, 144411, India.
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Jadhav A, Jagtap S, Vyavahare S, Sharbidre A, Kunchiraman B. Reviewing the potential of probiotics, prebiotics and synbiotics: advancements in treatment of ulcerative colitis. Front Cell Infect Microbiol 2023; 13:1268041. [PMID: 38145046 PMCID: PMC10739422 DOI: 10.3389/fcimb.2023.1268041] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2023] [Accepted: 11/22/2023] [Indexed: 12/26/2023] Open
Abstract
Inflammatory bowel diseases (IBD) like Crohn's and ulcerative colitis (UC) are multifactorial pathologies caused by environmental factors and genetic background. UC is a chronic inflammatory disorder that specifically targets the colon, resulting in inflammation. Various chemical interventions, including aminosalicylates, corticosteroids, immunomodulators, and biological therapies, have been extensively employed for the purpose of managing symptoms associated with UC. Nevertheless, it is important to note that these therapeutic interventions may give rise to undesirable consequences, including, but not limited to, the potential for weight gain, fluid retention, and heightened vulnerability to infections. Emerging therapeutic approaches for UC are costly due to their chronic nature. Alternatives like synbiotic therapy, combining prebiotics and probiotics, have gained attention for mitigating dysbiosis in UC patients. Prebiotics promote beneficial bacteria proliferation, while probiotics establish a balanced gut microbiota and regulate immune system functionality. The utilisation of synbiotics has been shown to improve the inflammatory response and promote the resolution of symptoms in individuals with UC through the stimulation of beneficial bacteria growth and the enhancement of intestinal barrier integrity. Hence, this review article aims to explore the potential benefits and underlying reasons for incorporating alternative approaches in the management of UC with studies performed using prebiotics, probiotics, and synbiotics to treat ulcerative colitis and to highlight safety and considerations in UC and future perspectives. This will facilitate the utilisation of novel treatment strategies for the safer and more efficacious management of patients with UC.
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Affiliation(s)
- Apurva Jadhav
- Herbal Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Suresh Jagtap
- Herbal Medicine, Interactive Research School for Health Affairs, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
| | - Suresh Vyavahare
- Sai Ayurved Medical College, Maharashtra University of Health Sciences, Solapur, Maharashtra, India
| | - Archana Sharbidre
- Department of Zoology, Savitribai Phule Pune University, Pune, Maharashtra, India
| | - Bipinraj Kunchiraman
- Microbial Biotechnology, Rajiv Gandhi Institute of IT & Biotechnology, Bharati Vidyapeeth (Deemed to be University), Pune, Maharashtra, India
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Mitra AK, Asala AF, Malone S, Mridha MK. Effects of Probiotics in Adults with Gastroenteritis: A Systematic Review and Meta-Analysis of Clinical Trials. Diseases 2023; 11:138. [PMID: 37873782 PMCID: PMC10594472 DOI: 10.3390/diseases11040138] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2023] [Revised: 10/06/2023] [Accepted: 10/09/2023] [Indexed: 10/25/2023] Open
Abstract
Probiotics have been widely used in gastroenteritis due to acute and chronic illnesses. However, evidence supporting the effectiveness of probiotics in different health conditions is inconclusive and conflicting. The aim of this study was to review the existing literature on the effects of probiotics on gastroenteritis among adults. Only original articles on clinical trials that demonstrated the effects of probiotics in adults with gastroenteritis were used for this analysis. Multiple databases, such as PubMed, Google Scholar, MEDLINE and Scopus databases, were searched for the data. The study followed standard procedures for data extraction using a PRISMA flow chart. A quality appraisal of the selected studies was conducted using CADIMA. Finally, a meta-analysis was performed. Thirty-five articles met the selection criteria; of them, probiotics were found effective in the treatment and/or prevention of chronic inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease in 17 (49%), and the treatment of pouchitis in 4 (11.4%), antibiotic-induced diarrhea in 3 (8.6%), Helicobacter pylori infection in 2 (5.7%) and diverticulitis in 1 (2.9%), while the remaining 7 (20%) were ineffective, and 1 study's results were inconclusive. The meta-analysis did not demonstrate any significant protective effects of probiotics. Having a τ2 value of zero and I2 of 6%, the studies were homogeneous and had minimum variances. Further studies are suggested to evaluate the beneficial effects of probiotics in IBDs and other chronic bowel diseases.
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Affiliation(s)
- Amal K. Mitra
- Department of Epidemiology and Biostatistics, College of Health Sciences, Jackson State University, Jackson, MS 39213, USA; (A.F.A.); (S.M.)
| | - Adetoun F. Asala
- Department of Epidemiology and Biostatistics, College of Health Sciences, Jackson State University, Jackson, MS 39213, USA; (A.F.A.); (S.M.)
- Office of Preventive Heath, Mississippi State Department of Health, Ridgeland, MS 39157, USA
| | - Shelia Malone
- Department of Epidemiology and Biostatistics, College of Health Sciences, Jackson State University, Jackson, MS 39213, USA; (A.F.A.); (S.M.)
| | - Malay Kanti Mridha
- Brac James P. Grant School of Public Health, Center for Non-Communicable Disease and Nutrition, Brac University, Dhaka 1213, Bangladesh;
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Zhang B, Fan X, Du H, Zhao M, Zhang Z, Zhu R, He B, Zhang Y, Li X, Li J, Gu N. Foodborne Carbon Dot Exposure Induces Insulin Resistance through Gut Microbiota Dysbiosis and Damaged Intestinal Mucus Layer. ACS NANO 2023; 17:6081-6094. [PMID: 36897192 DOI: 10.1021/acsnano.3c01005] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2023]
Abstract
Foodborne carbon dots (CDs), an emerging food nanocontaminant, are an increasing risk factor for metabolic toxicity in mammals. Here, we report that chronic CD exposure induced glucose metabolism disorders via disruption of the gut-liver axis in mice. 16s rRNA analysis demonstrated that CD exposure decreased the abundance of beneficial bacteria (Bacteroides, Coprococcus, and S24-7) and increased the abundance of harmful bacteria (Proteobacteria, Oscillospira, Desulfovibrionaceae, and Ruminococcaceae), as well as increased the Firmicutes/Bacteroidetes ratio. Mechanistically, the increased pro-inflammatory bacteria release the endotoxin lipopolysaccharide, which induces an intestinal inflammation and disruption of the intestinal mucus layer, activating systemic inflammation and inducing hepatic insulin resistance in mice via the TLR4/NFκB/MAPK signaling pathway. Furthermore, these changes were almost completely reversed by probiotics. Fecal microbiota transplantation from CD-exposed mice induced glucose intolerance, damaged liver function, intestinal mucus layer injury, hepatic inflammation, and insulin resistance in the recipient mice. However, microbiota-depleted mice exposed to CDs had normal levels of these biomarkers consistent with microbiota-depleted control mice, which revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance. Together, our findings revealed that gut microbiota dysbiosis contributes to CD-induced inflammation-mediated insulin resistance and attempted to elucidate the specific underlying mechanism. Furthermore, we emphasized the importance of assessing the hazards associated with foodborne CDs.
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Affiliation(s)
- Boya Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
- State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150006, China
| | - Xingpei Fan
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Haining Du
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Meimei Zhao
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Ziyi Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Ruijiao Zhu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Bo He
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Yuxia Zhang
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Xiaoyan Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Jiaxin Li
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
| | - Ning Gu
- School of Life Science and Technology, Harbin Institute of Technology, Harbin 150001, China
- State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150006, China
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Ma B, Gavzy SJ, Saxena V, Song Y, Piao W, Lwin HW, Lakhan R, Iyyathurai J, Li L, France M, Paluskievicz C, Shirkey MW, Hittle L, Munawwar A, Mongodin EF, Bromberg JS. Strain-specific alterations in gut microbiome and host immune responses elicited by tolerogenic Bifidobacterium pseudolongum. Sci Rep 2023; 13:1023. [PMID: 36658194 PMCID: PMC9852428 DOI: 10.1038/s41598-023-27706-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 01/06/2023] [Indexed: 01/20/2023] Open
Abstract
The beneficial effects attributed to Bifidobacterium are largely attributed to their immunomodulatory capabilities, which are likely to be species- and even strain-specific. However, their strain-specificity in direct and indirect immune modulation remain largely uncharacterized. We have shown that B. pseudolongum UMB-MBP-01, a murine isolate strain, is capable of suppressing inflammation and reducing fibrosis in vivo. To ascertain the mechanism driving this activity and to determine if it is specific to UMB-MBP-01, we compared it to a porcine tropic strain B. pseudolongum ATCC25526 using a combination of cell culture and in vivo experimentation and comparative genomics approaches. Despite many shared features, we demonstrate that these two strains possess distinct genetic repertoires in carbohydrate assimilation, differential activation signatures and cytokine responses signatures in innate immune cells, and differential effects on lymph node morphology with unique local and systemic leukocyte distribution. Importantly, the administration of each B. pseudolongum strain resulted in major divergence in the structure, composition, and function of gut microbiota. This was accompanied by markedly different changes in intestinal transcriptional activities, suggesting strain-specific modulation of the endogenous gut microbiota as a key to immune modulatory host responses. Our study demonstrated a single probiotic strain can influence local, regional, and systemic immunity through both innate and adaptive pathways in a strain-specific manner. It highlights the importance to investigate both the endogenous gut microbiome and the intestinal responses in response to probiotic supplementation, which underpins the mechanisms through which the probiotic strains drive the strain-specific effect to impact health outcomes.
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Affiliation(s)
- Bing Ma
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
| | - Samuel J Gavzy
- Department of Surgery, University of Maryland Medical Center, Baltimore, MD, 21201, USA
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Vikas Saxena
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Yang Song
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Wenji Piao
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Hnin Wai Lwin
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Ram Lakhan
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Jegan Iyyathurai
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Lushen Li
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Michael France
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Christina Paluskievicz
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Marina W Shirkey
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Lauren Hittle
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Arshi Munawwar
- Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
| | - Emmanuel F Mongodin
- Institute of Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA
- Division of Lung Diseases, National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), Bethesda, MD, USA
| | - Jonathan S Bromberg
- Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
- Department of Surgery, University of Maryland Medical Center, Baltimore, MD, 21201, USA.
- Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD, 21201, USA.
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10
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Cannon AR, Shim EH, Kuprys PV, Choudhry MA. IL-22 and Lactobacillus delbrueckii mitigate alcohol-induced exacerbation of DSS-induced colitis. J Leukoc Biol 2022; 112:1471-1484. [PMID: 35916052 PMCID: PMC9701151 DOI: 10.1002/jlb.4a0122-068r] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 06/29/2022] [Indexed: 01/04/2023] Open
Abstract
Ulcerative colitis (UC) is characterized by cycles of active disease flare and inactive disease remission. During UC remission, IL-22 is up-regulated, acting as a hallmark of entrance into UC remission. Recently, we found that in our mouse model of binge alcohol and dextran sodium sulfate (DSS)-induced colitis, alcohol increases severity of UC pathology. In this study, we assessed not only whether alcohol influenced IL-22 expression and thereby perpetuates UC, but also whether recombinant IL-22 (rIL-22) or treatment with a probiotic could alleviate exacerbated symptoms of UC. Levels of large intestine IL-22 were significantly decreased ∼6.9-fold in DSS ethanol compared with DSS vehicle. Examination of lamina propria (LP) cells in the large intestine revealed IL-22+ γδ T cells in DSS vehicle-treated mice were significantly increased, while IL-22+ γδ T cells in DSS ethanol mice were unable to mount this IL-22 response. We administered rIL-22 and found it restored weight loss of DSS ethanol-treated mice. Colonic shortening and increased Enterobacteriaceae were also attenuated. Administration of Lactobacillus delbrueckii attenuated weight loss (p < 0.01), colon length (p < 0.001), mitigated increases in Enterobacteriaceae, increased levels of IL-22, and increased levels of p-STAT3 back to that of DSS vehicle group in DSS ethanol mice. In contrast, sole administration of L. delbrueckii supernatant was not sufficient to reduce UC exacerbation following alcohol. Our findings suggest L. delbrueckii contributes to repair mechanisms by increasing levels of IL-22, resulting in phosphorylation of STAT3, thus attenuating the alcohol-induced increases in intestinal damage after colitis.
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Affiliation(s)
- Abigail R. Cannon
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
- Integrative Cell Biology Program, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
- Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
| | - Esther H. Shim
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
| | - Paulius V. Kuprys
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
| | - Mashkoor A. Choudhry
- Alcohol Research Program, Burn and Shock Trauma Research Institute, Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
- Integrative Cell Biology Program, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
- Department of Surgery, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
- Department of Microbiology and Immunology, Loyola University Chicago Health Sciences Campus, Maywood, IL 60153, USA
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11
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Geldenhuys J, Redelinghuys MJ, Lombaard HA, Ehlers MM, Cowan D, Kock MM. Diversity of the gut, vaginal and oral microbiome among pregnant women in South Africa with and without pre-eclampsia. Front Glob Womens Health 2022; 3:810673. [PMID: 36188424 PMCID: PMC9525020 DOI: 10.3389/fgwh.2022.810673] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2021] [Accepted: 07/29/2022] [Indexed: 11/13/2022] Open
Abstract
Background Changes in microbial communities are a known characteristic of various inflammatory diseases and have been linked to adverse pregnancy outcomes, such as preterm birth. However, there is a paucity of information regarding the taxonomic composition and/or diversity of microbial communities in pre-eclampsia. The aim of this study was to determine the diversity of the gut, vaginal and oral microbiome in a cohort of South African pregnant women with and without pre-eclampsia. The diversity of the gut, vaginal and oral microbiome was determined by targeted next generation sequencing (NGS) of the V3 and V4 region of the 16S rRNA gene on the Illumina MiSeq platform. Results In this study population, pre-eclampsia was associated with a significantly higher alpha diversity (P = 0.0472; indicated by the Shannon index) in the vaginal microbiome accompanied with a significant reduction in Lactobacillus spp. (P = 0.0275), compared to normotensive pregnant women. Lactobacillus iners was identified as the predominant species of the vaginal microbiome in both cohorts. High inter-individual variation in alpha diversity was observed in the gut and oral microbiome in both cohorts. Although differences in the relative abundance of bacteria at all phylogenetic levels were observed, overall microbial composition of the gut, oral and vaginal microbiome was not significantly different in the pre-eclampsia cohort compared to the normotensive cohort. Conclusion Collectively, a reduction of Lactobacillus spp., and predominance of L. iners in pregnant women with pre-eclampsia could suggest an unstable vaginal microbiome that might predispose pregnant women to develop pre-eclampsia. The lack of significant structural changes in the gut, oral and vaginal microbiome does not suggest that the characterized communities play a role in pre-eclampsia, but could indicate a characteristic unique to the study population. The current study provided novel information on the diversity of the gut, oral and vaginal microbiome among pregnant women in South Africa with and without pre-eclampsia. The current study provides a baseline for further investigations on the potential role of microbial communities in pre-eclampsia.
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Affiliation(s)
- Janri Geldenhuys
- Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Centre for Microbial Ecology and Genomics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
| | - Mathys J. Redelinghuys
- Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Centre for Microbial Ecology and Genomics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
| | - Hendrik A. Lombaard
- Obstetrics and Gynecology, Rahima Moosa Mother and Child Hospital, Wits Obstetrics and Gynecology Clinical Research Division, School of Clinical Medicine, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa
| | - Marthie M. Ehlers
- Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Centre for Microbial Ecology and Genomics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
- Department of Medical Microbiology, Tshwane Academic Division, National Health Laboratory Service, Pretoria, South Africa
| | - Don Cowan
- Centre for Microbial Ecology and Genomics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
| | - Marleen M. Kock
- Department of Medical Microbiology, Faculty of Health Sciences, University of Pretoria, Pretoria, South Africa
- Centre for Microbial Ecology and Genomics, Department of Biochemistry, Genetics and Microbiology, University of Pretoria, Pretoria, South Africa
- Department of Medical Microbiology, Tshwane Academic Division, National Health Laboratory Service, Pretoria, South Africa
- *Correspondence: Marleen M. Kock
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12
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Prasad R, Patton MJ, Floyd JL, Fortmann S, DuPont M, Harbour A, Wright J, Lamendella R, Stevens BR, Oudit GY, Grant MB. Plasma Microbiome in COVID-19 Subjects: An Indicator of Gut Barrier Defects and Dysbiosis. Int J Mol Sci 2022; 23:9141. [PMID: 36012406 PMCID: PMC9409329 DOI: 10.3390/ijms23169141] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2022] [Revised: 08/10/2022] [Accepted: 08/12/2022] [Indexed: 12/16/2022] Open
Abstract
The gut is a well-established route of infection and target for viral damage by SARS-CoV-2. This is supported by the clinical observation that about half of COVID-19 patients exhibit gastrointestinal (GI) complications. We aimed to investigate whether the analysis of plasma could provide insight into gut barrier dysfunction in patients with COVID-19 infection. Plasma samples of COVID-19 patients (n = 146) and healthy individuals (n = 47) were collected during hospitalization and routine visits. Plasma microbiome was analyzed using 16S rRNA sequencing and gut permeability markers including fatty acid binding protein 2 (FABP2), peptidoglycan (PGN), and lipopolysaccharide (LPS) in both patient cohorts. Plasma samples of both cohorts contained predominately Proteobacteria, Firmicutes, Bacteroides, and Actinobacteria. COVID-19 subjects exhibit significant dysbiosis (p = 0.001) of the plasma microbiome with increased abundance of Actinobacteria spp. (p = 0.0332), decreased abundance of Bacteroides spp. (p = 0.0003), and an increased Firmicutes:Bacteroidetes ratio (p = 0.0003) compared to healthy subjects. The concentration of the plasma gut permeability marker FABP2 (p = 0.0013) and the gut microbial antigens PGN (p < 0.0001) and LPS (p = 0.0049) were significantly elevated in COVID-19 patients compared to healthy subjects. These findings support the notion that the intestine may represent a source for bacteremia and contribute to worsening COVID-19 outcomes. Therapies targeting the gut and prevention of gut barrier defects may represent a strategy to improve outcomes in COVID-19 patients.
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Affiliation(s)
- Ram Prasad
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Michael John Patton
- Hugh Kaul Precision Medicine Institute, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA
| | - Jason Levi. Floyd
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Seth Fortmann
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Mariana DuPont
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | - Angela Harbour
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
| | | | | | - Bruce R. Stevens
- Department of Physiology and Functional Genomics, University of Florida, Gainesville, FL 32611, USA
| | - Gavin Y. Oudit
- Division of Cardiology, Department of Medicine, University of Alberta, Mazankowski Alberta Heart Institute, Edmonton, AB T6G 2B7, Canada
| | - Maria B. Grant
- Department of Ophthalmology and Visual Sciences, University of Alabama at Birmingham, 1670 University BLVD, VH490, Birmingham, AL 35294, USA
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13
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Foster-Nyarko E, Pallen MJ. The microbial ecology of Escherichia coli in the vertebrate gut. FEMS Microbiol Rev 2022; 46:fuac008. [PMID: 35134909 PMCID: PMC9075585 DOI: 10.1093/femsre/fuac008] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2021] [Revised: 01/31/2022] [Accepted: 02/01/2022] [Indexed: 11/13/2022] Open
Abstract
Escherichia coli has a rich history as biology's 'rock star', driving advances across many fields. In the wild, E. coli resides innocuously in the gut of humans and animals but is also a versatile pathogen commonly associated with intestinal and extraintestinal infections and antimicrobial resistance-including large foodborne outbreaks such as the one that swept across Europe in 2011, killing 54 individuals and causing approximately 4000 infections and 900 cases of haemolytic uraemic syndrome. Given that most E. coli are harmless gut colonizers, an important ecological question plaguing microbiologists is what makes E. coli an occasionally devastating pathogen? To address this question requires an enhanced understanding of the ecology of the organism as a commensal. Here, we review how our knowledge of the ecology and within-host diversity of this organism in the vertebrate gut has progressed in the 137 years since E. coli was first described. We also review current approaches to the study of within-host bacterial diversity. In closing, we discuss some of the outstanding questions yet to be addressed and prospects for future research.
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Affiliation(s)
- Ebenezer Foster-Nyarko
- Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom
- Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, NR4 7TJ, United Kingdom
- Department of Infection Biology, London School of Hygiene and Tropical Medicine, Keppel Street, London WC1E 7HT, United Kingdom
| | - Mark J Pallen
- Quadram Institute Bioscience, Norwich Research Park, Norwich, NR4 7UQ, United Kingdom
- School of Veterinary Medicine, University of Surrey, Guildford, Surrey, GU2 7AL, United Kingdom
- School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, NR4 7TU, United Kingdom
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14
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Hassan H, Kinsey S, Phillips B. Mucositis reduction with probiotics in children with cancer: a randomised-controlled feasibility study. Arch Dis Child 2022; 107:259-264. [PMID: 34193407 DOI: 10.1136/archdischild-2020-319968] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 06/22/2021] [Indexed: 11/04/2022]
Abstract
BACKGROUND A recent systematic review and meta-analysis identified a paucity of randomised-controlled trials (RCTs) investigating the use of probiotics to reduce or prevent mucositis and infection in children with cancer. OBJECTIVE This study evaluated the feasibility of undertaking an RCT and investigated the efficacy of probiotics for reducing or preventing mucositis and infection in children with cancers. SETTING The Paediatric Oncology and Haematology department at Leeds Teaching Hospital, UK. PATIENTS Children aged 1 year or older, receiving chemotherapies likely to cause mucositis. INTERVENTIONS Participants were randomised to receive the probiotic or placebo on day 1-14 of a chemotherapy cycle. Participants were also required to complete a patient diary for 21 days. MAIN OUTCOME MEASURES To assess whether it is feasible to recruit children diagnosed with cancer who are at risk of developing mucositis to an adequately powered RCT. RESULTS Between May and November 2019, 34 out of 39 eligible participants were approached. Ten patients were recruited (4 probiotic and 6 placebo) of which 2 participants withdrew. Seven participants partially completed the diary but only two participants completed 80% or more. Eligible participants appeared to prefer giving informal verbal feedback when in direct contact with research and healthcare professionals. CONCLUSION This study demonstrated that recruitment needs to be improved prior to undertaking an adequately powered RCT. TRIAL REGISTRATION NUMBER NCT03785938.
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Affiliation(s)
- Hadeel Hassan
- Leeds Institute of Cancer and Pathology, University of Leeds, Faculty of Medicine and Health, Leeds, UK
- Paediatric Haematology and Oncology, Leeds General Infirmary, Leeds, UK
| | - Sally Kinsey
- Leeds Institute of Cancer and Pathology, University of Leeds, Faculty of Medicine and Health, Leeds, UK
- Paediatric Haematology, Leeds General Infirmary, Leeds, West Yorkshire, UK
| | - Bob Phillips
- Centre for Reviews and Dissemination, University of York Alcuin College, York, UK
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15
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Hu Y, Ye Z, Wu M, She Y, Li L, Xu Y, Qin K, Hu Z, Yang M, Lu F, Ye Q. The Communication Between Intestinal Microbiota and Ulcerative Colitis: An Exploration of Pathogenesis, Animal Models, and Potential Therapeutic Strategies. Front Med (Lausanne) 2021; 8:766126. [PMID: 34966755 PMCID: PMC8710685 DOI: 10.3389/fmed.2021.766126] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Accepted: 11/18/2021] [Indexed: 12/12/2022] Open
Abstract
Ulcerative Colitis (UC) is a chronic inflammatory bowel disease. The prolonged course of UC and the lack of effective treatment management make it difficult to cure, affecting the health and life safety of patients. Although UC has received more attention, the etiology and pathogenesis of UC are still unclear. Therefore, it is urgent to establish an updated and comprehensive understanding of UC and explore effective treatment strategies. Notably, sufficient evidence shows that the intestinal microbiota plays an important role in the pathogenesis of UC, and the treating method aimed at improving the balance of the intestinal microbiota exhibits a therapeutic potential for UC. This article reviews the relationship between the genetic, immunological and microbial risk factors with UC. At the same time, the UC animal models related to intestinal microbiota dysbiosis induced by chemical drugs were evaluated. Finally, the potential value of the therapeutic strategies for restoring intestinal microbial homeostasis and treating UC were also investigated. Comprehensively, this study may help to carry out preclinical research, treatment theory and methods, and health management strategy of UC, and provide some theoretical basis for TCM in the treatment of UC.
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Affiliation(s)
- Yu Hu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhen Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mingquan Wu
- Department of Pharmacy, Sichuan Provincial Orthopedic Hospital, Chengdu, China
| | - Yingqi She
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Linzhen Li
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yujie Xu
- Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Kaihua Qin
- Health Preservation and Rehabilitation College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Zhipeng Hu
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Maoyi Yang
- Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Fating Lu
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qiaobo Ye
- School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine, Chengdu, China
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16
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Liu Y, Zhou M, Yang M, Jin C, Song Y, Chen J, Gao M, Ai Z, Su D. Pulsatilla chinensis Saponins Ameliorate Inflammation and DSS-Induced Ulcerative Colitis in Rats by Regulating the Composition and Diversity of Intestinal Flora. Front Cell Infect Microbiol 2021; 11:728929. [PMID: 34804990 PMCID: PMC8602866 DOI: 10.3389/fcimb.2021.728929] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 10/01/2021] [Indexed: 12/19/2022] Open
Abstract
Pulsatilla chinensis (Bunge) Regel is a commonly used Chinese medicine for clearing away heat and detoxification, cooling blood, stopping dysentery, and anti-inflammatory effects. Pulsatilla chinensis saponins (PRS) have been identified to be responsible for producing these pharmacological activities. Studies have shown that Pulsatilla decoction has a good therapeutic effect on ulcerative colitis (UC), however, the therapeutic effect of PRS on UC has not been reported. Therefore, the purpose of this study was to investigate the possible anti-UC activity of PRS using a dextran sulfate sodium (DSS)-induced rat model, and further study the mechanism of PRS in the treatment of UC. The fecal and colon samples were collected from rats to monitor the changes in the composition and diversity of the intestinal flora, and pathological colon sections were also made to examine the mesenteric hemorheological characteristics. The results showed that PRS significantly reduced the mesenteric blood flow in UC rats and significantly alleviated the inflammatory response, which indicates that saponins are involved in the anti-UC effects of PRS. At the same time, it is also suggested that the regulation of intestinal flora by Pulsatilla chinensis saponins is an important pathway for its anti-UC activity, which may be ascribed to the increase in beneficial bacteria like norank_F_Muribaculaceae and norank_F_norank_O_Clostridia_UCG-014, and decrease in the harmful Bacteroides.
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Affiliation(s)
- Yali Liu
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China.,Department of Pharmacy, Nanchang Medical College, Nanchang, China
| | - Mingyue Zhou
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Ming Yang
- Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, State Key Lab of Innovation Drug and Efficient Energy-Saving Pharmaceutical Equipment, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Chen Jin
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Yonggui Song
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Jingbin Chen
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Meng Gao
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Zhifu Ai
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
| | - Dan Su
- Key Laboratory of Depression Animal Model Based on Traditional Chinese Medicine (TCM) Syndrome, Jiangxi Administration of Traditional Chinese Medicine, Key Laboratory of TCM for Prevention and Treatment of Brain Diseases with Cognitive Impairment, Jiangxi University of Chinese Medicine, Nanchang, China
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17
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Rousseau RK, Walmsley SL, Lee T, Rosenes R, Reinhard RJ, Malazogu F, Benko E, Huibner S, Kovacs CM, Singer J, Kim CJ, Kaul R. A randomized, blinded, placebo-controlled trial of De Simone formulation probiotic during HIV-associated suboptimal CD4+ T cell recovery. J Acquir Immune Defic Syndr 2021; 89:199-207. [PMID: 34693932 DOI: 10.1097/qai.0000000000002840] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 10/04/2021] [Indexed: 11/25/2022]
Abstract
OBJECTIVE To assess whether probiotic supplementation may reduce disease-linked systemic immune activation in people living with HIV with the immunologic non-responder (INR) phenotype. DESIGN Phase 2b, randomized, double-blind, placebo-controlled pilot trial. METHODS HIV-positive individuals with blood CD4+ T cell counts <350/mm3 despite viral suppression were randomized 2:1 to receive De Simone Formulation Probiotic (DSFP; "Visbiome" commercially) or placebo for 48 weeks; target enrolment was 36 patients. The primary endpoint was change in blood CD8+ T cell co-expression of HLA-DR and CD38 ("CD8 activation"). Secondary endpoints included biomarkers of inflammation, immune reconstitution, bacterial translocation, and gut permeability. Adjusted linear regression and linear mixed methods regression evaluated the differences between study arms from baseline to week 48. Study monitoring was done by the CIHR Canadian HIV Trials Network Data Safety Monitoring Committee. RESULTS Nineteen patients received DSFP, while 10 received placebo. One probiotic-arm patient withdrew early. Blood CD8 activation increased 0.82 percentage points (pp) in the probiotic arm (95% confidence interval [CI];-1.23,2.87;) and decreased by 2.06pp in the placebo arm (-4.81,0.70; between arms p=0.097). CD4+ T cell activation (%HLA-DR+) decreased in the placebo arm (-3.79pp [-7.32,-0.26]) but increased in the probiotic arm (1.64 [-0.98,4.26]; between arms p=0.018). No differences were observed in plasma or urine biomarkers of inflammation or microbial translocation. CONCLUSIONS Blood immune activation markers in INR individuals on effective ART were not reduced by supplementation with DSFP; CD4+ T cell activation may have been increased.
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Affiliation(s)
- Rodney K Rousseau
- University of Toronto, Departments of Immunology, Medicine, and Internal Medicine, Toronto, Canada University Health Network, Toronto General Hospital Immunodeficiency Clinic, Toronto, Canada Toronto General Hospital Research Institute, Toronto, Canada CIHR Canadian HIV Trials Network, Vancouver, Canada Centre for Health Evaluation & Outcomes Sciences, Vancouver, Canada Community Health Advocate and Consultant (Independent), Toronto, Canada Public/Global Health Consultant (Independent), San Francisco, USA Maple Leaf Medical Clinic, Toronto, Canada
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18
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Del Río Castillo AE, De León-Rodriguez A, Terrones M, Barba de la Rosa AP. Multi-walled carbon nanotubes enhance the genetic transformation of Bifidobacterium longum. CARBON 2021; 184:902-909. [DOI: 10.1016/j.carbon.2021.08.052] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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19
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Zhang Y, Li A. High-throughput virtual screening and microsecond MD simulations to identify potential sugar mimic of the solute-binding protein BlAXBP of the ABC transporter from Bifidobacterium animalis subsp. Lactis. Comput Biol Chem 2021; 93:107541. [PMID: 34273720 DOI: 10.1016/j.compbiolchem.2021.107541] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Revised: 07/02/2021] [Accepted: 07/03/2021] [Indexed: 12/08/2022]
Abstract
Xylotetraose is a prebiotic oligosaccharide can be utilized by the ABC transporter of the gut microbiota Bifidobacteria. BlAXBP is the solute binding protein of the ABC transporter, and its complex with xylotetraose has been solved by X-ray crystallography. Here, we have identified novel sugar mimic of BlAXBP by applying a high-throughput virtual screening of ZINC database containing a huge library with ∼22 M compounds. To begin with, we identified 18,571 ligands by a ligand-based virtual screening. Further, a total of 3968 compounds were selected for molecular docking due to their Tanimoto coefficient's value were larger than a cutoff of 0.08. The molecular mechanics-generalized born surface area was used to evaluate the binding free energies, and the top 10 ligands with free energies below an energy threshold of -35.22 kcal/mol were selected. ZINC13783511 formed the most stable complex with BlAXBP and its recognition mechanism were further explored by microsecond MD simulations in explicit solvent. Free energy landscapes were used to evaluate conformational changes of BlAXBP in its ligand free and binding states. Collectively, this work identified potential novel sugar mimics to BlAXBP, providing novel atomic-level understanding of the binding mechanism.
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Affiliation(s)
- Yubo Zhang
- Department of Food Science, Foshan University, Foshan, 528231, China.
| | - Anqi Li
- Department of Food Science, Foshan University, Foshan, 528231, China
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20
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Ciaravolo S, Martínez-López LM, Allcock RJN, Woodward AP, Mansfield C. Longitudinal Survey of Fecal Microbiota in Healthy Dogs Administered a Commercial Probiotic. Front Vet Sci 2021; 8:664318. [PMID: 34235200 PMCID: PMC8255976 DOI: 10.3389/fvets.2021.664318] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2021] [Accepted: 05/25/2021] [Indexed: 12/12/2022] Open
Abstract
The aim of this longitudinal microbiome study was to investigate the effects of a commercially available veterinary synbiotic product (Blackmore's® Paw DigestiCare 60™) on the fecal microbiome of healthy dogs using 16S rRNA gene microbial profiling. Fifteen healthy, privately-owned dogs participated in a 2-week trial administration of the product. Fecal samples were collected at different time points, including baseline (prior to treatment), during administration and after discontinuation of product. Large intra- and inter-individual variation was observed throughout the study, but microbiome composition at higher phylogenetic levels, alpha and beta diversity were not significantly altered after 2 weeks of probiotic administration, suggesting an absence of probiotic impact on microbial diversity. Administration of the synbiotic preparation did, however, result in transient increases in probiotic species from Enterococacceae and Streptococacceae families as well as an increase in Fusobacteria; with the fecal microbiota partially reverting to its baseline state 3-weeks after cessation of probiotic administration.
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Affiliation(s)
- Susan Ciaravolo
- Department of Veterinary Clinical Sciences, Melbourne Veterinary School, The University of Melbourne, Werribee, VIC, Australia.,Peninsula Vet, Emergency and Referral Hospital, Mornington, VIC, Australia
| | - Lina María Martínez-López
- Department of Veterinary Clinical Sciences, Melbourne Veterinary School, The University of Melbourne, Werribee, VIC, Australia
| | - Richard J N Allcock
- School of Biomedical Sciences, The University of Western Australia, Perth, WA, Australia
| | - Andrew P Woodward
- Department of Veterinary Clinical Sciences, Melbourne Veterinary School, The University of Melbourne, Werribee, VIC, Australia.,Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Werribee, VIC, Australia
| | - Caroline Mansfield
- Department of Veterinary Clinical Sciences, Melbourne Veterinary School, The University of Melbourne, Werribee, VIC, Australia
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21
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Engevik MA, Danhof HA, Hall A, Engevik KA, Horvath TD, Haidacher SJ, Hoch KM, Endres BT, Bajaj M, Garey KW, Britton RA, Spinler JK, Haag AM, Versalovic J. The metabolic profile of Bifidobacterium dentium reflects its status as a human gut commensal. BMC Microbiol 2021; 21:154. [PMID: 34030655 PMCID: PMC8145834 DOI: 10.1186/s12866-021-02166-6] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 03/30/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Bifidobacteria are commensal microbes of the mammalian gastrointestinal tract. In this study, we aimed to identify the intestinal colonization mechanisms and key metabolic pathways implemented by Bifidobacterium dentium. RESULTS B. dentium displayed acid resistance, with high viability over a pH range from 4 to 7; findings that correlated to the expression of Na+/H+ antiporters within the B. dentium genome. B. dentium was found to adhere to human MUC2+ mucus and harbor mucin-binding proteins. Using microbial phenotyping microarrays and fully-defined media, we demonstrated that in the absence of glucose, B. dentium could metabolize a variety of nutrient sources. Many of these nutrient sources were plant-based, suggesting that B. dentium can consume dietary substances. In contrast to other bifidobacteria, B. dentium was largely unable to grow on compounds found in human mucus; a finding that was supported by its glycosyl hydrolase (GH) profile. Of the proteins identified in B. dentium by proteomic analysis, a large cohort of proteins were associated with diverse metabolic pathways, indicating metabolic plasticity which supports colonization of the dynamic gastrointestinal environment. CONCLUSIONS Taken together, we conclude that B. dentium is well adapted for commensalism in the gastrointestinal tract.
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Affiliation(s)
- Melinda A Engevik
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA.
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA.
- Department of Regernative Medicine & Cell Biology, Medical University of South Carolina, SC, Charleston, USA.
| | - Heather A Danhof
- Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Anne Hall
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Kristen A Engevik
- Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Thomas D Horvath
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Sigmund J Haidacher
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Kathleen M Hoch
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Bradley T Endres
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA
| | - Meghna Bajaj
- Department of Chemistry and Physics, and Department of Biotechnology, Alcorn State University, Lorman, MS, 39096, USA
| | - Kevin W Garey
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, TX, USA
| | - Robert A Britton
- Department of Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA
| | - Jennifer K Spinler
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - Anthony M Haag
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
| | - James Versalovic
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX, USA
- Department of Pathology, Texas Children's Hospital, Houston, TX, USA
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22
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Armstrong H, Mander I, Zhang Z, Armstrong D, Wine E. Not All Fibers Are Born Equal; Variable Response to Dietary Fiber Subtypes in IBD. Front Pediatr 2021; 8:620189. [PMID: 33520902 PMCID: PMC7844368 DOI: 10.3389/fped.2020.620189] [Citation(s) in RCA: 55] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Accepted: 12/10/2020] [Indexed: 12/12/2022] Open
Abstract
Diet provides a safe and attractive alternative to available treatment options in a variety of diseases; however, research has only just begun to elucidate the role of diet in chronic diseases, such as the inflammatory bowel diseases (IBD). The chronic and highly debilitating IBDs, Crohn disease and ulcerative colitis, are hallmarked by intestinal inflammation, immune dysregulation, and dysbiosis; and evidence supports a role for genetics, microbiota, and the environment, including diet, in disease pathogenesis. This is true especially in children with IBD, where diet-based treatments have shown excellent results. One interesting group of dietary factors that readily links microbiota to gut health is dietary fibers. Fibers are not digested by human cells, but rather fermented by the gut microbes within the bowel. Evidence has been mounting over the last decade in support of the importance of dietary fibers in the maintenance of gut health and in IBD; however, more recent studies highlight the complexity of this interaction and importance of understanding the role of each individual dietary fiber subtype, especially during disease. There are roughly ten subtypes of dietary fibers described to date, categorized as soluble or insoluble, with varying chemical structures, and large differences in their fermentation profiles. Many studies to date have described the benefits of the byproducts of fermentation in healthy individuals and the potential health benefits in select disease models. However, there remains a void in our understanding of how each of these individual fibers affect human health in dysbiotic settings where appropriate fermentation may not be achieved. This review highlights the possibilities for better defining the role of individual dietary fibers for use in regulating inflammation in IBD.
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Affiliation(s)
- Heather Armstrong
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, Canada
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
| | - Inderdeep Mander
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, Canada
| | - Zhengxiao Zhang
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, Canada
- Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - David Armstrong
- Department of Chemical and Physical Sciences, University of Toronto Mississauga, Mississauga, ON, Canada
| | - Eytan Wine
- Centre of Excellence for Gastrointestinal Inflammation and Immunity Research, University of Alberta, Edmonton, AB, Canada
- Department of Pediatrics, University of Alberta, Edmonton, AB, Canada
- Department of Physiology, University of Alberta, Edmonton, AB, Canada
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23
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Poletti M, Arnauts K, Ferrante M, Korcsmaros T. Organoid-based Models to Study the Role of Host-microbiota Interactions in IBD. J Crohns Colitis 2020; 15:1222-1235. [PMID: 33341879 PMCID: PMC8256633 DOI: 10.1093/ecco-jcc/jjaa257] [Citation(s) in RCA: 43] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
The gut microbiota appears to play a central role in health, and alterations in the gut microbiota are observed in both forms of inflammatory bowel disease [IBD], namely Crohn's disease and ulcerative colitis. Yet, the mechanisms behind host-microbiota interactions in IBD, especially at the intestinal epithelial cell level, are not yet fully understood. Dissecting the role of host-microbiota interactions in disease onset and progression is pivotal, and requires representative models mimicking the gastrointestinal ecosystem, including the intestinal epithelium, the gut microbiota, and immune cells. New advancements in organoid microfluidics technology are facilitating the study of IBD-related microbial-epithelial cross-talk, and the discovery of novel microbial therapies. Here, we review different organoid-based ex vivo models that are currently available, and benchmark their suitability and limitations for specific research questions. Organoid applications, such as patient-derived organoid biobanks for microbial screening and 'omics technologies, are discussed, highlighting their potential to gain better mechanistic insights into disease mechanisms and eventually allow personalised medicine.
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Affiliation(s)
- Martina Poletti
- Earlham Institute, Norwich Research Park, Norwich, UK,Quadram Institute, Norwich Research Park, Norwich, UK
| | - Kaline Arnauts
- Department of Chronic Diseases, Metabolism and Ageing [CHROMETA], Translational Research Center for Gastrointestinal Disorders [TARGID], KU Leuven, Leuven, Belgium,Department of Development and Regeneration, Stem Cell Institute Leuven [SCIL], KU Leuven, Leuven, Belgium
| | - Marc Ferrante
- Department of Chronic Diseases, Metabolism and Ageing [CHROMETA], Translational Research Center for Gastrointestinal Disorders [TARGID], KU Leuven, Leuven, Belgium,Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium,Corresponding author: Marc Ferrante, MD, PhD, Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel.: +32 16 344225;
| | - Tamas Korcsmaros
- Earlham Institute, Norwich Research Park, Norwich, UK,Quadram Institute, Norwich Research Park, Norwich, UK
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24
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Zou Y, Chen T. Engineered Akkermansia muciniphila: A promising agent against diseases (Review). Exp Ther Med 2020; 20:285. [PMID: 33209129 PMCID: PMC7668130 DOI: 10.3892/etm.2020.9415] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 09/15/2020] [Indexed: 12/23/2022] Open
Abstract
Achieving a harmonious gut microbial ecosystem has been hypothesized to be a successful method for alleviating metabolic disorders. The administration of probiotics, such as Lactobacillus and Bifidobacteria, is a known traditional and safe pathway to regulate human commensal microbes. With advancements in genetic sequencing and genetic editing tools, more bacteria are able to function as engineered probiotics with multiple therapeutic properties. As one of the next-generation probiotic candidates, Akkermansia muciniphila (A. muciniphila) has been discovered to enhance the gut barrier function and moderate inflammatory responses, exhibit improved effects with pasteurization and display beneficial probiotic effects in individuals with obesity, type 2 diabetes, atherosclerosis and autism-related gastrointestinal disturbances. In view of this knowledge, the present review aimed to summarize the effects of A. muciniphila in the treatment of metabolic disorders and to discuss several mature recombination systems for the genetic modification of A. muciniphila. From gaining an enhanced understanding of its genetic background, ingested A. muciniphila is expected to be used in various applications, including as a diagnostic tool, and in the site-specific delivery of therapeutic drugs.
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Affiliation(s)
- Yixuan Zou
- Institute of Translational Medicine, National Engineering Research Center for Bioengineering Drugs and Technologies, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
| | - Tingtao Chen
- Institute of Translational Medicine, National Engineering Research Center for Bioengineering Drugs and Technologies, Nanchang University, Nanchang, Jiangxi 330031, P.R. China
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25
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Schierová D, Březina J, Mrázek J, Fliegerová KO, Kvasnová S, Bajer L, Drastich P. Gut Microbiome Changes in Patients with Active Left-Sided Ulcerative Colitis after Fecal Microbiome Transplantation and Topical 5-aminosalicylic Acid Therapy. Cells 2020; 9:cells9102283. [PMID: 33066233 PMCID: PMC7602113 DOI: 10.3390/cells9102283] [Citation(s) in RCA: 45] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Revised: 10/01/2020] [Accepted: 10/09/2020] [Indexed: 12/12/2022] Open
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease, and intestinal bacteria are implicated in the pathogenesis of this disorder. The administration of aminosalicylates (5-ASA) is a conventional treatment that targets the mucosa, while fecal microbial transplantation (FMT) is a novel treatment that directly targets the gut microbiota. The aim of this study was to identify changes in fecal bacterial composition after both types of treatments and evaluate clinical responses. Sixteen patients with active left-sided UC underwent enema treatment using 5-ASA (n = 8) or FMT (n = 8) with a stool from a single donor. Fecal microbiota were analyzed by 16S rDNA high-throughput sequencing, and clinical indices were used to assess the efficacy of treatments. 5-ASA therapy resulted in clinical remission in 50% (4/8) of patients, but no correlation with changes in fecal bacteria was observed. In FMT, remission was achieved in 37.5% (3/8) of patients and was associated with a significantly increased relative abundance of the families Lachnospiraceae, Ruminococcaceae, and Clostridiaceae of the phylum Firmicutes, and Bifidobacteriaceae and Coriobacteriaceae of the phylum Actinobacteria. At the genus level, Faecalibacterium, Blautia, Coriobacteria, Collinsela, Slackia, and Bifidobacterium were significantly more frequent in patients who reached clinical remission. However, the increased abundance of beneficial taxa was not a sufficient factor to achieve clinical improvement in all UC patients. Nevertheless, our preliminary results indicate that FMT as non-drug-using method is thought to be a promising treatment for UC patients.
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Affiliation(s)
- Dagmar Schierová
- Institute of Animal Physiology and Genetics of the Czech Academy of Science, v.v.i., 142 20 Prague, Czech Republic; (K.O.F.); (S.K.)
- Correspondence: (D.S.); (J.M.); Tel.: +420-2-6709-0509 (D.S.); +420-2-6709-0506 (J.M.)
| | - Jan Březina
- Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (J.B.); (L.B.); (P.D.)
| | - Jakub Mrázek
- Institute of Animal Physiology and Genetics of the Czech Academy of Science, v.v.i., 142 20 Prague, Czech Republic; (K.O.F.); (S.K.)
- Correspondence: (D.S.); (J.M.); Tel.: +420-2-6709-0509 (D.S.); +420-2-6709-0506 (J.M.)
| | - Kateřina Olša Fliegerová
- Institute of Animal Physiology and Genetics of the Czech Academy of Science, v.v.i., 142 20 Prague, Czech Republic; (K.O.F.); (S.K.)
| | - Simona Kvasnová
- Institute of Animal Physiology and Genetics of the Czech Academy of Science, v.v.i., 142 20 Prague, Czech Republic; (K.O.F.); (S.K.)
| | - Lukáš Bajer
- Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (J.B.); (L.B.); (P.D.)
| | - Pavel Drastich
- Hepatogastroenterology Department, Institute for Clinical and Experimental Medicine, 140 21 Prague, Czech Republic; (J.B.); (L.B.); (P.D.)
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26
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Metin M, Altun A, Köylüoğlu G. The effect of probiotics on ıntestinal motility in an experimental short bowel model. Acta Cir Bras 2020; 35:e202000804. [PMID: 32901681 PMCID: PMC7478466 DOI: 10.1590/s0102-865020200080000004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Accepted: 07/24/2020] [Indexed: 12/23/2022] Open
Abstract
PURPOSE To investigate the effect of probiotics on spontaneous contractions of smooth muscle isolated from jejunum and ileum of rat model. METHODS Four rat groups were created (n=8, in each) including control (Group 1), control+probiotic (Group 2), short bowel (Group 3), and short bowel+probiotic (Group 4). Groups 1 and 2 underwent sham operation, Groups 3 and 4 underwent massive bowel resection. Bifidobacterium Lactis was administered in Groups 2 and 4 daily (P.O.) for three weeks. On postoperative week 3, rats were sacrificed, and jejunum and ileum smooth muscle were isolated for organ bath. Muscle contraction changes were analyzed before and after addition of antagonists. RESULTS Short bowel group exhibited increased amplitude and frequency of spontaneous contractions. The addition of probiotics significantly decreased enhanced amplitude and frequency of bowel contraction in short bowel group and returned to control values. L-NNA increased amplitude and frequency of contractions in all groups. While indomethacin and nimesulide increased the amplitude in all groups, the frequency was only increased in jejunum. Hexamethonium and tetrodotoxin did not change the contraction characteristics in all groups. CONCLUSION We suggest that early use of probiotics may significantly regulate bowel motility, and accordingly improve absorption of nutrients in short bowel syndrome.
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Affiliation(s)
- Mehmet Metin
- Cumhuriyet University, Turkey; Hitit University Erol Olçok Training and Research Hospital, Turkey
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27
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Microbiota Changes Due to Grape Seed Extract Diet Improved Intestinal Homeostasis and Decreased Fatness in Parental Broiler Hens. Microorganisms 2020; 8:microorganisms8081141. [PMID: 32731511 PMCID: PMC7465624 DOI: 10.3390/microorganisms8081141] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 07/25/2020] [Accepted: 07/27/2020] [Indexed: 11/16/2022] Open
Abstract
In poultry, the selection of broilers for growth performance has induced a deterioration in the health of the parental hens associated with poor reproductive efficiency. To improve these parameters, we administered to laying parental broiler hens a regular diet supplemented or not (Control) with a moderate (1%) or a high level (2%) of grape seed extract (GSE). The 1% GSE diet was administered from a young age (from 4 to 40 weeks of age) and the high level of 2% GSE was administered only during a 2-week period (from 38 to 40 weeks of age) in the laying period. The analysis of 40-week-old hens showed that 2% GSE displayed a reduction in the fat tissue and an improvement in fertility with heavier and more resistant eggs. Seven monomer phenolic metabolites of GSE were significantly measured in the plasma of the 2% GSE hens. GSE supplementation increased the relative abundance of the following bacteria populations: Bifidobacteriaceae, Lactobacilliaceae and Lachnospiraceae. In conclusion, a supplementation period of only 2 weeks with 2% GSE is sufficient to improve the metabolic and laying parameters of breeder hens through a modification in the microbiota.
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28
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Streptococcus thermophilus: To Survive, or Not to Survive the Gastrointestinal Tract, That Is the Question! Nutrients 2020; 12:nu12082175. [PMID: 32708008 PMCID: PMC7468695 DOI: 10.3390/nu12082175] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 07/17/2020] [Accepted: 07/20/2020] [Indexed: 01/05/2023] Open
Abstract
The probiotic market is increasing world-wide as well as the number of products marketed as probiotics. Among the latter, many products contain Streptococcus thermophilus strains at several dosages. However, the scientific evidence that should support the probiotic status of those S. thermophilus strains is often contradictory. This review analyses the scientific literature aimed to assess the ability of S. thermophilus strains to survive the human gastrointestinal tract by discussing the scientific validity of the methods applied for the bacterial recovery and identification from stool samples. This review highlights that in most of the intervention studies reviewed, the identification of S. thermophilus strains from stools was not carried out with the necessary taxonomic accuracy to avoid their misidentification with Streptococcus salivarius, a common human commensal and a species phylogenetically close to S. thermophilus. Moreover, this review highlights how critical the accurate taxonomic identification of S. thermophilus in metagenomics-based studies can be.
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29
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Ren C, Faas MM, de Vos P. Disease managing capacities and mechanisms of host effects of lactic acid bacteria. Crit Rev Food Sci Nutr 2020; 61:1365-1393. [PMID: 32366110 DOI: 10.1080/10408398.2020.1758625] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Consumption of lactic acid bacteria (LAB) has been suggested to confer health-promoting effects on the host. However, effects of LABs have been reported to be species- and strain-specific and the mechanisms involved are subjects of discussion. Here, the possible mechanisms by which LABs induce antipathogenic, gut barrier enhancing and immune modulating effects in consumers are reviewed. Specific strains for which it has been proven that health is improved by these mechanisms are discussed. However, most strains probably act via several or combinations of mechanisms depending on which effector molecules they express. Current insight is that these effector molecules are either present on the cell wall of LAB or are excreted. These molecules are reviewed as well as the ligand binding receptors in the host. Also postbiotics are discussed. Finally, we provide an overview of the efficacy of LABs in combating infections caused by Helicobacter pylori, Salmonella, Escherichia coli, Streptococcus pneumoniae, and influenza virus, in controlling gut inflammatory diseases, in managing allergic disorders, and in alleviating cancer.
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Affiliation(s)
- Chengcheng Ren
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Marijke M Faas
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
| | - Paul de Vos
- Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands
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30
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Cheng FS, Pan D, Chang B, Jiang M, Sang LX. Probiotic mixture VSL#3: An overview of basic and clinical studies in chronic diseases. World J Clin Cases 2020; 8:1361-1384. [PMID: 32368530 PMCID: PMC7190945 DOI: 10.12998/wjcc.v8.i8.1361] [Citation(s) in RCA: 78] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2019] [Revised: 03/27/2020] [Accepted: 04/08/2020] [Indexed: 02/05/2023] Open
Abstract
Probiotics are known as “live microorganisms” and have been proven to have a health effect on hosts at the proper dose. Recently, a kind of probiotic mixture including eight live bacterial strains, VSL#3, has attracted considerable attention for its combined effect. VSL#3 is the only probiotic considered as a kind of medical food; it mainly participates in the regulation of the intestinal barrier function, including improving tight junction protein function, balancing intestinal microbial composition, regulating immune-related cytokine expression and so on. The objective of this review is to discuss the treatment action and mechanism for the administration of VSL#3 in chronic diseases of animals and humans (including children). We found that VSL#3 has a therapeutic or preventive effect in various systemic diseases per a large number of studies, including digestive systemic diseases (gastrointestinal diseases and hepatic diseases), obesity and diabetes, allergic diseases, nervous systemic diseases, atherosclerosis, bone diseases, and female reproductive systemic diseases.
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Affiliation(s)
- Fang-Shu Cheng
- Department of Dermatology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China
- Class 85 of 101k, China Medical University, Shenyang 110004, Liaoning Province, China
| | - Dan Pan
- Department of Geriatrics, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Bing Chang
- Department of Gastroenterology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Min Jiang
- Department of Gastroenterology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
| | - Li-Xuan Sang
- Department of Geriatrics, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning Province, China
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31
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Iheozor-Ejiofor Z, Kaur L, Gordon M, Baines PA, Sinopoulou V, Akobeng AK. Probiotics for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev 2020; 3:CD007443. [PMID: 32128794 PMCID: PMC7059960 DOI: 10.1002/14651858.cd007443.pub3] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND Ulcerative colitis is an inflammatory condition affecting the colon, with an annual incidence of approximately 10 to 20 per 100,000 people. The majority of people with ulcerative colitis can be put into remission, leaving a group who do not respond to first- or second-line therapies. There is a significant proportion of people who experience adverse effects with current therapies. Consequently, new alternatives for the treatment of ulcerative colitis are constantly being sought. Probiotics are live microbial feed supplements that may beneficially affect the host by improving intestinal microbial balance, enhancing gut barrier function and improving local immune response. OBJECTIVES The primary objective was to determine the efficacy of probiotics compared to placebo, no treatment, or any other intervention for the maintenance of remission in people with ulcerative colitis. The secondary objective was to assess the occurrence of adverse events associated with the use of probiotics. SEARCH METHODS We searched CENTRAL, MEDLINE, Embase, and two other databases on 31 October 2019. We contacted authors of relevant studies and manufacturers of probiotics regarding ongoing or unpublished trials that may be relevant to the review, and we searched ClinicalTrials.gov. We also searched references of trials for any additional trials. SELECTION CRITERIA Randomised controlled trials (RCTs) that compared probiotics against placebo or any other intervention, in both adults and children, for the maintenance of remission in ulcerative colitis were eligible for inclusion. Maintenance therapy had to be for a minimum of three months when remission has been established by any clinical, endoscopic,histological or radiological relapse as defined by study authors. DATA COLLECTION AND ANALYSIS Two review authors independently conducted data extraction and 'Risk of bias' assessment of included studies. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS In this review, we included 12 studies (1473 randomised participants) that met the inclusion criteria. Participants were mostly adults. The studies compared probiotics to placebo, probiotics to 5-aminosalicylic acid (5-ASA) and a combination of probiotics and 5-ASA to 5-ASA. The studies ranged in length from 12 to 52 weeks. The average age of participants was between 32 and 51, with a range between 18 and 88 years. Seven studies investigated a single bacterial strain, and five studies considered mixed preparations of multiple strains. The risk of bias was high in all except three studies due to selective reporting, incomplete outcome data and lack of blinding. This resulted in low- to very low-certainty of evidence. It is uncertain if there is any difference in occurrence of clinical relapse when probiotics are compared with placebo (RR 0.87, 95% CI 0.63 to 1.18; 4 studies, 361 participants; very low-certainty evidence (downgraded for risk of bias, imbalance in baseline characteristics and imprecision)). It is also uncertain whether probiotics lead to a difference in the number of people who maintain clinical remission compared with placebo (RR 1.16, 95% CI 0.98 to 1.37; 2 studies, 141 participants; very low-certainty evidence (downgraded for risk of bias, imbalance in baseline characteristics and imprecision)). When probiotics are compared with 5-ASA, there may be little or no difference in clinical relapse (RR 1.01, 95% CI 0.84 to 1.22; 2 studies, 452 participants; low-certainty evidence) and maintenance of clinical remission (RR 1.06, 95% CI 0.90 to 1.25; 1 study, 125 participants; low-certainty evidence). It is uncertain if there is any difference in clinical relapse when probiotics, combined with 5-ASA are compared with 5-ASA alone (RR 1.11, 95% CI 0.66 to 1.87; 2 studies, 242 participants; very low-certainty evidence (downgraded due to risk of bias and imprecision)). There may be little or no difference in maintenance of remission when probiotics, combined with 5-ASA, are compared with 5-ASA alone (RR 1.05, 95% CI 0.89 to 1.24; 1 study, 122 participants; low-certainty evidence). Where reported, most of the studies which compared probiotics with placebo recorded no serious adverse events or withdrawals due to adverse events. For the comparison of probiotics and 5-ASA, one trial reported 11/110 withdrawals due to adverse events with probiotics and 11/112 with 5-ASA (RR 1.02, 95% CI 0.46 to 2.25; 222 participants; very low-certainty evidence). Discontinuation of therapy was due to gastrointestinal symptoms. One study (24 participants) comparing probiotics combined with 5-ASA with 5-ASA alone, reported no withdrawals due to adverse events; and two studies reported two withdrawals in the probiotic arm, due to avascular necrosis of bilateral femoral head and pulmonary thromboembolism (RR 5.29, 95% CI 0.26 to 107.63; 127 participants; very low-certainty evidence). Health-related quality of life and need for additional therapy were reported infrequently. AUTHORS' CONCLUSIONS The effectiveness of probiotics for the maintenance of remission in ulcerative colitis remains unclear. This is due to low- to very low-certainty evidence from poorly conducted studies, which contribute limited amounts of data from a small number of participants. Future trials comparing probiotics with 5-ASA rather than placebo will better reflect conventional care given to people with ulcerative colitis. Appropriately powered studies with a minimum length of 12 months are needed.
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Affiliation(s)
- Zipporah Iheozor-Ejiofor
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
| | - Lakhbir Kaur
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
| | - Morris Gordon
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
- Blackpool Victoria Hospital, Families Division, Blackpool, UK
| | | | - Vasiliki Sinopoulou
- University of Central Lancashire, School of Medicine, Harrington Building, Preston, Lancashire, UK
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Horvath A, Leber B, Feldbacher N, Steinwender M, Komarova I, Rainer F, Blesl A, Stadlbauer V. The effects of a multispecies synbiotic on microbiome-related side effects of long-term proton pump inhibitor use: A pilot study. Sci Rep 2020; 10:2723. [PMID: 32066847 PMCID: PMC7026433 DOI: 10.1038/s41598-020-59550-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2019] [Accepted: 01/30/2020] [Indexed: 02/07/2023] Open
Abstract
Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (−18.8 ng/mg; 95%CI: −50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (−46.3 ng/mg; 95%CI: −71.4; −21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.
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Affiliation(s)
- Angela Horvath
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria. .,Center for Biomarker Research in Medicine (CBmed), Graz, Austria.
| | - Bettina Leber
- Division of Transplantation Surgery, Medical University of Graz, Graz, Austria
| | - Nicole Feldbacher
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria.,Center for Biomarker Research in Medicine (CBmed), Graz, Austria
| | - Markus Steinwender
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Irina Komarova
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Florian Rainer
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Andreas Blesl
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
| | - Vanessa Stadlbauer
- Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
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Naseer M, Poola S, Ali S, Samiullah S, Tahan V. Prebiotics and Probiotics in Inflammatory Bowel Disease: Where are we now and where are we going? CURRENT CLINICAL PHARMACOLOGY 2020; 15:216-233. [PMID: 32164516 DOI: 10.2174/1574884715666200312100237] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/29/2019] [Revised: 01/17/2020] [Accepted: 01/28/2020] [Indexed: 02/08/2023]
Abstract
The incidence, prevalence, and cost of care associated with diagnosis and management of inflammatory bowel disease are on the rise. The role of gut microbiota in the causation of Crohn's disease and ulcerative colitis has not been established yet. Nevertheless, several animal models and human studies point towards the association. Targeting intestinal dysbiosis for remission induction, maintenance, and relapse prevention is an attractive treatment approach with minimal adverse effects. However, the data is still conflicting. The purpose of this article is to provide the most comprehensive and updated review on the utility of prebiotics and probiotics in the management of active Crohn's disease and ulcerative colitis/pouchitis and their role in the remission induction, maintenance, and relapse prevention. A thorough literature review was performed on PubMed, Ovid Medline, and EMBASE using the terms "prebiotics AND ulcerative colitis", "probiotics AND ulcerative colitis", "prebiotics AND Crohn's disease", "probiotics AND Crohn's disease", "probiotics AND acute pouchitis", "probiotics AND chronic pouchitis" and "prebiotics AND pouchitis". Observational studies and clinical trials conducted on humans and published in the English language were included. A total of 71 clinical trials evaluating the utility of prebiotics and probiotics in the management of inflammatory bowel disease were reviewed and the findings were summarized. Most of these studies on probiotics evaluated lactobacillus, De Simone Formulation or Escherichia coli Nissle 1917 and there is some evidence supporting these agents for induction and maintenance of remission in ulcerative colitis and prevention of pouchitis relapse with minimal adverse effects. The efficacy of prebiotics such as fructooligosaccharides and Plantago ovata seeds in ulcerative colitis are inconclusive and the data regarding the utility of prebiotics in pouchitis is limited. The results of the clinical trials for remission induction and maintenance in active Crohn's disease or post-operative relapse with probiotics and prebiotics are inadequate and not very convincing. Prebiotics and probiotics are safe, effective and have great therapeutic potential. However, better designed clinical trials in the multicenter setting with a large sample and long duration of intervention are needed to identify the specific strain or combination of probiotics and prebiotics which will be more beneficial and effective in patients with inflammatory bowel disease.
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Affiliation(s)
- Maliha Naseer
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, East Carolina University, Greenville, NC 27834, United States
| | - Shiva Poola
- Department of Internal and Pediatric Medicine, East Carolina University, Greenville, NC 27834, United States
| | - Syed Ali
- Department of Internal Medicine, University of Missouri, Columbia, MO 65211, United States
| | - Sami Samiullah
- Assistant Professor of Clinical Medicine, University of Missouri, Division of Gastroenterology and Hepatology, Columbia, MO 65211, United States
| | - Veysel Tahan
- Assistant Professor of Clinical Medicine, University of Missouri, Division of Gastroenterology and Hepatology, Columbia, MO 65211, United States
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Katsuki R, Sakata S, Nakao R, Oishi K, Nakamura Y. Lactobacillus curvatus CP2998 Prevents Dexamethasone-Induced Muscle Atrophy in C2C12 Myotubes. J Nutr Sci Vitaminol (Tokyo) 2019; 65:455-458. [PMID: 31666484 DOI: 10.3177/jnsv.65.455] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/27/2022]
Abstract
To investigate whether heat-killed Lactobacillus curvatus CP2998 (CP2998) inhibits glucocorticoid-induced myotube atrophy which is associated with the ubiquitin-proteasome system, mouse skeletal muscle C2C12 myotubes were treated with dexamethasone (DEX) in the presence or absence of CP2998. DEX exposure significantly decreased myotube diameters and increased mRNA expression levels of MuRF1 and MAFbx, E3 ubiquitin ligases. CP2998 treatment restored myotube diameters and dose dependently decreased mRNA expression levels of these E3 ubiquitin ligases. CP2998 treatment also inhibited DEX-induced glucocorticoid dependent transcription. Our results suggest that CP2998 prevents DEX-induced muscle atrophy by suppressing glucocorticoid receptor activation.
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Affiliation(s)
- Ryo Katsuki
- Department of Lactic Acid Bacteria Technology Core Technology Laboratories, Asahi Quality & Innovations, Ltd
| | - Shinji Sakata
- Department of Lactic Acid Bacteria Technology Core Technology Laboratories, Asahi Quality & Innovations, Ltd
| | - Reiko Nakao
- Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST)
| | - Katsutaka Oishi
- Biological Clock Research Group, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST).,Department of Applied Biological Science, Graduate School of Science and Technology, Tokyo University of Science.,Department of Computational and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo.,School of Integrative and Global Majors (SIGMA), University of Tsukuba
| | - Yasunori Nakamura
- Department of Lactic Acid Bacteria Technology Core Technology Laboratories, Asahi Quality & Innovations, Ltd
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Ngo N, Choucair K, Creeden JF, Qaqish H, Bhavsar K, Murphy C, Lian K, Albrethsen MT, Stanbery L, Phinney RC, Brunicardi FC, Dworkin L, Nemunaitis J. Bifidobacterium spp: the promising Trojan Horse in the era of precision oncology. Future Oncol 2019; 15:3861-3876. [PMID: 31668087 DOI: 10.2217/fon-2019-0374] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Selective delivery of therapeutic agents into solid tumors has been a major challenge impeding the achievement of long-term disease remission and cure. The need to develop alternative drug delivery routes to achieve higher drug concentration in tumor tissue, reduce unwanted off-target side effects and thus achieve greater therapeutic efficacy, has resulted in an explosive body of research. Bifidobacterium spp. are anaerobic, nonpathogenic, Gram-positive bacteria, commensal to the human gut that are a possible anticancer drug-delivery vehicle. In this review, we describe Bifidobacterium's microbiology, current clinical applications, overview of the preclinical work investigating Bifidobacterium's potential to deliver anticancer therapy, and review the different strategies used up to date. Finally, we discuss both current challenges and future prospects.
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Affiliation(s)
- Nealie Ngo
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Khalil Choucair
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Justin F Creeden
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Hanan Qaqish
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Krupa Bhavsar
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Chantal Murphy
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Kendra Lian
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Mary T Albrethsen
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Laura Stanbery
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | | | - F Charles Brunicardi
- Department of Surgery, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - Lance Dworkin
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
| | - John Nemunaitis
- Department of Medicine, University of Toledo College of Medicine & Life Sciences, Toledo, OH 43614, USA
- ProMedica Health System, Toledo, OH 43606, USA
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Probiotic Lactobacillus and Bifidobacterium strains possess safety characteristics, antiviral activities and host adherence factors revealed by genome mining. EPMA J 2019; 10:337-350. [PMID: 31832110 DOI: 10.1007/s13167-019-00184-z] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 08/11/2019] [Indexed: 02/07/2023]
Abstract
Background Probiotics belonging to Lactobacillus and Bifidobacterium spp. have been exploited for their health benefits in treatment and prevention of many pathological conditions and promoting human health. Recent advances in understanding probiotics-human interaction through microbiome research in the context of various medical conditions suggest their provisional role in preventive, personalized, and predictive medicine. To streamline their application in disease prevention, development of personalized-based treatments, or their use as biomarkers for predictive diagnosis, in vitro screening for strains with potential probiotic properties should be performed. In this work, we aimed to emphasize the probiotic features of four Lactobacillus and two Bifidobacterium probiotic strains which showed antagonistic properties against microbial pathogens. Methods Firstly, cytotoxicity assessment of cell-free preparations from these strains was performed using a baby hamster kidney (BHK) cells and cell viability was measured by means of sulfo-rhodamine B stain. Secondly, Newcastle disease (ND) and infectious bursal disease (IBD) viruses which pose a great threat in infected poultry were used for assessing antiviral activity of probiotics. Thirdly, the genomes of six probiotic strains were used to identify genes encoding host adherence factors that mediate interaction with human tissues. Results Probiotic preparations exhibited insignificant toxicity as indicated by the high survival rate of BHK cells (surviving fraction varied from 0.82 to 0.99) as compared to the untreated control. Cell-free preparations of probiotics mixed with equal volume of ND and IBD viruses (106 and 104 Tissue Culture Infectious Dose 50, respectively) reduced the titer of ND and IBD viruses on chicken embryo fibroblast cells. Genome mining analysis revealed that the draft genomes of these strains were predicted to encode LPXTG-containing proteins, surface layer proteins, tight adherence pili, sortase-dependent pili, fibronectin, or collagen binding proteins and other factors that adhere to human tissues such as mucus. Such adherence factors enable probiotic bacteria to interact and colonize the host. Conclusion Taken together, safety privileges, antiviral activities, and genomically encoded host interaction factors confirmed probiotic features of the six probiotic strains and their potential in promoting human health.
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Khan I, Ullah N, Zha L, Bai Y, Khan A, Zhao T, Che T, Zhang C. Alteration of Gut Microbiota in Inflammatory Bowel Disease (IBD): Cause or Consequence? IBD Treatment Targeting the Gut Microbiome. Pathogens 2019; 8:pathogens8030126. [PMID: 31412603 PMCID: PMC6789542 DOI: 10.3390/pathogens8030126] [Citation(s) in RCA: 495] [Impact Index Per Article: 82.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 08/03/2019] [Accepted: 08/05/2019] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic complex inflammatory gut pathological condition, examples of which include Crohn’s disease (CD) and ulcerative colitis (UC), which is associated with significant morbidity. Although the etiology of IBD is unknown, gut microbiota alteration (dysbiosis) is considered a novel factor involved in the pathogenesis of IBD. The gut microbiota acts as a metabolic organ and contributes to human health by performing various physiological functions; deviation in the gut flora composition is involved in various disease pathologies, including IBD. This review aims to summarize the current knowledge of gut microbiota alteration in IBD and how this contributes to intestinal inflammation, as well as explore the potential role of gut microbiota-based treatment approaches for the prevention and treatment of IBD. The current literature has clearly demonstrated a perturbation of the gut microbiota in IBD patients and mice colitis models, but a clear causal link of cause and effect has not yet been presented. In addition, gut microbiota-based therapeutic approaches have also shown good evidence of their effects in the amelioration of colitis in animal models (mice) and IBD patients, which indicates that gut flora might be a new promising therapeutic target for the treatment of IBD. However, insufficient data and confusing results from previous studies have led to a failure to define a core microbiome associated with IBD and the hidden mechanism of pathogenesis, which suggests that well-designed randomized control trials and mouse models are required for further research. In addition, a better understanding of this ecosystem will also determine the role of prebiotics and probiotics as therapeutic agents in the management of IBD.
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Affiliation(s)
- Israr Khan
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Naeem Ullah
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Lajia Zha
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Yanrui Bai
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Ashiq Khan
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Probiotics and Biological Feed Research Center, Lanzhou University, Lanzhou 730000, China
| | - Tang Zhao
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China
| | - Tuanjie Che
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou 730000, China
| | - Chunjiang Zhang
- School of Life Sciences, Lanzhou University, Lanzhou 730000, China.
- Key Laboratory of Cell Activities and Stress Adaptations, Ministry of Education, Lanzhou University, Lanzhou 730000, China.
- Gansu Key Laboratory of Biomonitoring and Bioremediation for Environmental Pollution, Lanzhou University, Lanzhou 730000, China.
- Gansu Key Laboratory of Functional Genomics and Molecular Diagnosis, Lanzhou 730000, China.
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Engevik MA, Luk B, Chang-Graham AL, Hall A, Herrmann B, Ruan W, Endres BT, Shi Z, Garey KW, Hyser JM, Versalovic J. Bifidobacterium dentium Fortifies the Intestinal Mucus Layer via Autophagy and Calcium Signaling Pathways. mBio 2019; 10:e01087-19. [PMID: 31213556 PMCID: PMC6581858 DOI: 10.1128/mbio.01087-19] [Citation(s) in RCA: 171] [Impact Index Per Article: 28.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2019] [Accepted: 05/11/2019] [Indexed: 02/07/2023] Open
Abstract
Much remains unknown about how the intestinal microbiome interfaces with the protective intestinal mucus layer. Bifidobacterium species colonize the intestinal mucus layer and can modulate mucus production by goblet cells. However, select Bifidobacterium strains can also degrade protective glycans on mucin proteins. We hypothesized that the human-derived species Bifidobacterium dentium would increase intestinal mucus synthesis and expulsion, without extensive degradation of mucin glycans. In silico data revealed that B. dentium lacked the enzymes necessary to extensively degrade mucin glycans. This finding was confirmed by demonstrating that B. dentium could not use naive mucin glycans as primary carbon sources in vitro To examine B. dentium mucus modulation in vivo, Swiss Webster germfree mice were monoassociated with live or heat-killed B. dentium Live B. dentium-monoassociated mice exhibited increased colonic expression of goblet cell markers Krüppel-like factor 4 (Klf4), Trefoil factor 3 (Tff3), Relm-β, Muc2, and several glycosyltransferases compared to both heat-killed B. dentium and germfree counterparts. Likewise, live B. dentium-monoassociated colon had increased acidic mucin-filled goblet cells, as denoted by Periodic Acid-Schiff-Alcian Blue (PAS-AB) staining and MUC2 immunostaining. In vitro, B. dentium-secreted products, including acetate, were able to increase MUC2 levels in T84 cells. We also identified that B. dentium-secreted products, such as γ-aminobutyric acid (GABA), stimulated autophagy-mediated calcium signaling and MUC2 release. This work illustrates that B. dentium is capable of enhancing the intestinal mucus layer and goblet cell function via upregulation of gene expression and autophagy signaling pathways, with a net increase in mucin production.IMPORTANCE Microbe-host interactions in the intestine occur along the mucus-covered epithelium. In the gastrointestinal tract, mucus is composed of glycan-covered proteins, or mucins, which are secreted by goblet cells to form a protective gel-like structure above the epithelium. Low levels of mucin or alterations in mucin glycans are associated with inflammation and colitis in mice and humans. Although current literature links microbes to the modulation of goblet cells and mucins, the molecular pathways involved are not yet fully understood. Using a combination of gnotobiotic mice and mucus-secreting cell lines, we have identified a human-derived microbe, Bifidobacterium dentium, which adheres to intestinal mucus and secretes metabolites that upregulate the major mucin MUC2 and modulate goblet cell function. Unlike other Bifidobacterium species, B. dentium does not extensively degrade mucin glycans and cannot grow on mucin alone. This work points to the potential of using B. dentium and similar mucin-friendly microbes as therapeutic agents for intestinal disorders with disruptions in the mucus barrier.
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Affiliation(s)
- Melinda A Engevik
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Berkley Luk
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Alexandra L Chang-Graham
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - Anne Hall
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Beatrice Herrmann
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Wenly Ruan
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Bradley T Endres
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| | - Zhongcheng Shi
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
| | - Kevin W Garey
- Department of Pharmacy Practice and Translational Research, University of Houston College of Pharmacy, Houston, Texas, USA
| | - Joseph M Hyser
- Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA
| | - James Versalovic
- Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA
- Department of Pathology, Texas Children's Hospital, Houston, Texas, USA
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De Angelis M, Scagnolari C, Oliva A, Cavallari EN, Celani L, Santinelli L, Innocenti GP, Borrazzo C, Ceccarelli G, Vullo V, d'Ettorre G. Short-Term Probiotic Administration Increases Fecal-Anti Candida Activity in Healthy Subjects. Microorganisms 2019; 7:E162. [PMID: 31163660 PMCID: PMC6616593 DOI: 10.3390/microorganisms7060162] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Revised: 05/20/2019] [Accepted: 05/27/2019] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Candida albicans' ability to evade host immune responses represents a serious threat for vulnerable patients. OBJECTIVES To investigate if (1) feces from healthy subjects exert anti-Candida activity; (2) fecal anti-Candida activity is modified by probiotic administration and (3) different probiotic differently modulate anti-Candida activity. PATIENTS AND METHODS Feces from healthy donors were analyzed before and after seven days of dietary supplementation with two different probiotic formulations (VSL#3®; Vivomixx®). Candida albicans was cultured with decreasing concentrations of diluted feces, obtained before and after the treatment period. The relationship between anti-Candida activity of feces, interferon-α, anti-interferon-α antibodies and the expression of MxA, ISG15 and IFNAR1 was also evaluated. RESULTS Feces obtained prior to probiotic intake and feces collected after supplementation with VSL#3® did not affect Candida albicans growth. On the contrary, a 3log10 inhibition of Candida development was observed after Vivomixx® intake. Interferon-α played a role in the inhibition of Candida growth. CONCLUSION Fecal anti-Candida activity was not observed prior to probiotic supplementation. Seven days of administration of Vivomixx® increased fecal anti-Candida activity, the same effect was not observed after intake of VSL#3®. The probiotic-induced anti-Candida activity seems to be related to an increased local production and release of interferon-α. Clinical trials are needed to determine if a short pretreatment with specific probiotic formulations may increase anti-Candida defenses in patients at risk.
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Affiliation(s)
- Massimiliano De Angelis
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Carolina Scagnolari
- Department of Experimental Medicine- Virology section, University of Rome-Sapienza, Rome 00185, Italy.
| | - Alessandra Oliva
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Eugenio Nelson Cavallari
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Luigi Celani
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Letizia Santinelli
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Giuseppe Pietro Innocenti
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Cristian Borrazzo
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Giancarlo Ceccarelli
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Vincenzo Vullo
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
| | - Gabriella d'Ettorre
- Department of Public Health and Infectious Diseases, University of Rome-Sapienza, Rome 00185, Italy.
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Wang Y, Hatabu T. Mulberry juice freeze-dried powder attenuates the disease severity by the maintaining of colon mucosa in mice with DSS-induced acute colitis. Biosci Biotechnol Biochem 2019; 83:914-922. [DOI: 10.1080/09168451.2019.1580135] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
ABSTRACT
This study aimed to evaluate the microbial compositions and gene expression related to inflammation in dextran sodium sulfate (DSS)-induced acute colitis and the effect of mulberry supplementation. Male BALB/c mice received a diet supplemented with mulberry juice freeze-dried powder (MFP) or not for 3 weeks. After 3 weeks, the mice received water containing 5% (w/v) DSS or not for 1 week. The disease activity index score in mice fed MFP was significantly decreased. A significant decrease in Bifidobacterium spp. and the Clostridium perfringens subgroup was observed in mice not fed MFP. The number of goblet cell and NLRP6 expression were observed in mice fed a diet supplemented with MFP compared with mice not fed MFP. These results may indicate that mulberry mitigates DSS-induced acute colitis by a changing the gut microbial flora and by improving mucosal conditions.
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Affiliation(s)
- Yang Wang
- Laboratory of Animal Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan
| | - Toshimitsu Hatabu
- Laboratory of Animal Physiology, Graduate School of Environmental and Life Science, Okayama University, Okayama, Japan
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Fahmy CA, Gamal-Eldeen AM, El-Hussieny EA, Raafat BM, Mehanna NS, Talaat RM, Shaaban MT. Bifidobacterium longum Suppresses Murine Colorectal Cancer through the Modulation of oncomiRs and Tumor Suppressor miRNAs. Nutr Cancer 2019; 71:688-700. [PMID: 30862187 DOI: 10.1080/01635581.2019.1577984] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
The modulatory role of the Bifidobacterium longum (BL), isolated from women breast milk, on some oncogenic and tumor suppressor miRNAs as well as IL-1β and IL6 targeted-miRNAs was investigated using murine colorectal cancer (CRC) induced on the top of inflammatory ulcerative colitis model. The investigation of the oncomiRs miR-21a and miR-155, which regulate IL-6 and IL-1β expression, indicated that both was depressed by BL-administration in healthy and in CRC-mice. BL-administration induced the tumor suppressor miRNAs (miR-145 and miR-15a) expression in both of the healthy and in CRC-mice. The miR-146a expression, which regulates both of IL-1β and IL-6 expression, was decreased after the BL-administration in both of the healthy and in CRC-mice. In CRC-mice, NF-Kb concentration was elevated, however this NF-Kb induction was diminished after the treatment with BL. BL highly enhanced the IL-1β and IL-6 mRNA and protein concentrations in healthy mice. The administration of BL to CRC-mice resulted in a dramatic increase in IL-1β mRNA and IL-1β concentration, which in contrast was accompanied with a decrease in the IL-6 mRNA and IL-6 concentration. BL-administration resulted in a drop in the aberrant crypt foci number in CRC-mice and increased necrosis and fibrosis of the colon cells. The modulatory influence of B. longum on microRNAs may provide an important therapeutic impact in CRC through inhibition of the proliferation, invasion, apoptosis, and cell cycle of tumor cells.
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Affiliation(s)
- Cinderella A Fahmy
- a Cancer Biology and Genetics Laboratory , Centre of Excellence for Advanced Sciences, National Research Centre , Dokki , Cairo, Egypt.,b Biochemistry Department , National Research Centre , Dokki , Cairo, Egypt
| | - Amira M Gamal-Eldeen
- a Cancer Biology and Genetics Laboratory , Centre of Excellence for Advanced Sciences, National Research Centre , Dokki , Cairo, Egypt.,b Biochemistry Department , National Research Centre , Dokki , Cairo, Egypt.,c cClinical Laboratory Department, College of Applied Medical Sciences, Taif University, KSA
| | - Enas A El-Hussieny
- d Zoology Department, Faculty of Science , Ain Shams University , Cairo , Egypt
| | - Bassem M Raafat
- b Biochemistry Department , National Research Centre , Dokki , Cairo, Egypt.,e Radiological Sciences Department, College of Applied Medical Sciences , Taif University , KSA
| | - Nayra S Mehanna
- f f Dairy Science and Technology Department , National Research Centre , Cairo , Egypt
| | - Roba M Talaat
- g Department of Molecular Biology, Genetic Engineering and Biotechnology Research Institute , Sadat City University , Sadat City, Egypt
| | - Mohamed T Shaaban
- h h Botany Department, Faculty of Science , Menofiya University , Egypt
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Meng X, Zhou HY, Shen HH, Lufumpa E, Li XM, Guo B, Li BZ. Microbe-metabolite-host axis, two-way action in the pathogenesis and treatment of human autoimmunity. Autoimmun Rev 2019; 18:455-475. [PMID: 30844549 DOI: 10.1016/j.autrev.2019.03.006] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Accepted: 11/05/2018] [Indexed: 12/14/2022]
Abstract
The role of microorganism in human diseases cannot be ignored. These microorganisms have evolved together with humans and worked together with body's mechanism to maintain immune and metabolic function. Emerging evidence shows that gut microbe and their metabolites open up new doors for the study of human response mechanism. The complexity and interdependence of these microbe-metabolite-host interactions are rapidly being elucidated. There are various changes of microbial levels in models or in patients of various autoimmune diseases (AIDs). In addition, the relevant metabolites involved in mechanism mainly include short-chain fatty acids (SCFAs), bile acids (BAs), and polysaccharide A (PSA). Meanwhile, the interaction between microbes and host genes is also a factor that must be considered. It has been demonstrated that human microbes are involved in the development of a variety of AIDs, including organ-specific AIDs and systemic AIDs. At the same time, microbes or related products can be used to remodel body's response to alleviate or cure diseases. This review summarizes the latest research of microbes and their related metabolites in AIDs. More importantly, it highlights novel and potential therapeutics, including fecal microbial transplantation, probiotics, prebiotics, and synbiotics. Nonetheless, exact mechanisms still remain elusive, and future research will focus on finding a specific strain that can act as a biomarker of an autoimmune disease.
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Affiliation(s)
- Xiang Meng
- School of Stomatology, Anhui Medical University, Hefei, Anhui, China
| | - Hao-Yue Zhou
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China
| | - Hui-Hui Shen
- Department of Clinical Medicine, The second School of Clinical Medicine, Anhui Medical University, Anhui, Hefei, China
| | - Eniya Lufumpa
- Institute of Applied Health Research, University of Birmingham, Birmingham, UK
| | - Xiao-Mei Li
- Department of Rheumatology & Immunology, Anhui Provincial Hospital, Anhui, Hefei, China
| | - Biao Guo
- The Second Affiliated Hospital of Anhui Medical University, Anhui, Hefei, China
| | - Bao-Zhu Li
- Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Anhui Province Key Laboratory of Major Autoimmune Diseases, 81 Meishan Road, Hefei, Anhui, China.
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Astó E, Méndez I, Audivert S, Farran-Codina A, Espadaler J. The Efficacy of Probiotics, Prebiotic Inulin-Type Fructans, and Synbiotics in Human Ulcerative Colitis: A Systematic Review and Meta-Analysis. Nutrients 2019; 11:nu11020293. [PMID: 30704039 PMCID: PMC6412539 DOI: 10.3390/nu11020293] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2018] [Revised: 01/17/2019] [Accepted: 01/29/2019] [Indexed: 12/19/2022] Open
Abstract
Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13–2.15, p-value = 0.007, I2 = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23–2.43, p-value = 0.002, I2 = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.
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Affiliation(s)
- Erola Astó
- AB-Biotics, S.A., ESADE Creapolis, Av. Torre Blanca, 57, Sant Cugat del Vallès, E-08172 Barcelona, Spain.
| | - Iago Méndez
- AB-Biotics, S.A., ESADE Creapolis, Av. Torre Blanca, 57, Sant Cugat del Vallès, E-08172 Barcelona, Spain.
| | - Sergi Audivert
- AB-Biotics, S.A., ESADE Creapolis, Av. Torre Blanca, 57, Sant Cugat del Vallès, E-08172 Barcelona, Spain.
| | - Andreu Farran-Codina
- Department of Nutrition, Food Science, and Gastronomy, XaRTA ⁻ INSA, Faculty of Pharmacy, University of Barcelona, Campus de l'Alimentació de Torribera, Av. Prat de la Riba, 171, Santa Coloma de Gramenet, E-08921 Barcelona, Spain.
| | - Jordi Espadaler
- AB-Biotics, S.A., ESADE Creapolis, Av. Torre Blanca, 57, Sant Cugat del Vallès, E-08172 Barcelona, Spain.
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The Microbiome in Patients With Inflammatory Diseases. Clin Gastroenterol Hepatol 2019; 17:243-255. [PMID: 30196163 DOI: 10.1016/j.cgh.2018.08.078] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2018] [Revised: 08/17/2018] [Accepted: 08/24/2018] [Indexed: 02/07/2023]
Abstract
Microbial dysbiosis characterized by alterations in the structure and function of the gut microbiome has long been implicated in the pathogenesis of inflammatory bowel disease (IBD). To date, most human IBD microbiome studies are focused on microbial composition rather than function, however, with the latest technical advancements complemented by the rapidly dropping costs, studies focusing on the functional aspects of microbial dysbiosis are on the rise. Several compelling and complimentary pieces of evidence support the notion that the gut microbiome and their metabolites play an important role in the development of IBD. Data from preclinical studies overwhelmingly support the notion that changes in the gut microbiome causally underlie IBD pathogenesis. Hence, there is considerable interest in modulating the state and function of the gut microbiome to achieve therapeutic benefits. While the causal potential of the gut microbiome remains an active area of current research in the clinical setting, accumulating correlative evidence support the view that microbial dysbiosis parallels increased incidence of IBD. In this review, we intend to provide a brief overview of the current human IBD microbiome findings, describe the cause-effect relationships between the gut microbiome and IBD, and discuss the possibility of using microbiome-based approaches in the diagnosis, therapy, and management of disease. In addition, the potential role of microbiome-based interventions in the treatment of human IBD is also discussed.
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Bozzi Cionci N, Baffoni L, Gaggìa F, Di Gioia D. Therapeutic Microbiology: The Role of Bifidobacterium breve as Food Supplement for the Prevention/Treatment of Paediatric Diseases. Nutrients 2018; 10:E1723. [PMID: 30423810 PMCID: PMC6265827 DOI: 10.3390/nu10111723] [Citation(s) in RCA: 65] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2018] [Revised: 11/05/2018] [Accepted: 11/08/2018] [Indexed: 02/07/2023] Open
Abstract
The human intestinal microbiota, establishing a symbiotic relationship with the host, plays a significant role for human health. It is also well known that a disease status is frequently characterized by a dysbiotic condition of the gut microbiota. A probiotic treatment can represent an alternative therapy for enteric disorders and human pathologies not apparently linked to the gastrointestinal tract. Among bifidobacteria, strains of the species Bifidobacterium breve are widely used in paediatrics. B. breve is the dominant species in the gut of breast-fed infants and it has also been isolated from human milk. It has antimicrobial activity against human pathogens, it does not possess transmissible antibiotic resistance traits, it is not cytotoxic and it has immuno-stimulating abilities. This review describes the applications of B. breve strains mainly for the prevention/treatment of paediatric pathologies. The target pathologies range from widespread gut diseases, including diarrhoea and infant colics, to celiac disease, obesity, allergic and neurological disorders. Moreover, B. breve strains are used for the prevention of side infections in preterm newborns and during antibiotic treatments or chemotherapy. With this documentation, we hope to increase knowledge on this species to boost the interest in the emerging discipline known as "therapeutic microbiology".
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Affiliation(s)
- Nicole Bozzi Cionci
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
| | - Loredana Baffoni
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
| | - Francesca Gaggìa
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
| | - Diana Di Gioia
- Department of Agricultural and Food Sciences (DISTAL), Alma Mater Studiorum-Università di Bologna, Viale Fanin 42, 40127 Bologna, Italy.
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Guzman-Rodriguez M, McDonald JAK, Hyde R, Allen-Vercoe E, Claud EC, Sheth PM, Petrof EO. Using bioreactors to study the effects of drugs on the human microbiota. Methods 2018; 149:31-41. [PMID: 30102990 DOI: 10.1016/j.ymeth.2018.08.003] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2018] [Revised: 08/03/2018] [Accepted: 08/07/2018] [Indexed: 02/07/2023] Open
Abstract
The study of complex microbial communities has become a major research focus as mounting evidence suggests the pivotal role microbial communities play in host health and disease. Microbial communities of the gastrointestinal tract, known as the gut microbiota, have been implicated in aiding the host with vitamin biosynthesis, regulation of host energy metabolism, immune system development, and resistance to pathogen invasion. Conversely, disruptions of the gut microbiota have been linked to host morbidity, including the development of inflammatory diseases, metabolic disorders, increased cardiovascular risk, and increased risk of infectious diseases. However, studying the gut microbiota in humans and animals is challenging, as many microorganisms are fastidious with unique nutritional or environmental requirements that are often not met using conventional culture techniques. Bioreactors provide a unique solution to overcome some of the limitations of conventional culture techniques. Bioreactors have been used to propagate and establish complex microbial communities in vitro by recapitulating the physiological conditions found in the GI tract. These systems further our understanding of microbial physiology and facilitate our understanding of the impact of medications and xenobiotics on microbial communities. Here, we review the versatility and breadth of bioreactor systems that are currently available and how they are being used to study faecal and defined microbial communities. Bioreactors provide a unique opportunity to study complex microbial interactions and perturbations in vitro in a controlled environment without confounding biotic and abiotic variables.
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Affiliation(s)
- Mabel Guzman-Rodriguez
- Gastrointestinal Disease Research Unit, Kingston Health Sciences Center, Kingston, ON, Canada
| | - Julie A K McDonald
- Division of Integrative Systems Medicine and Digestive Disease, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, London, UK
| | - Richard Hyde
- Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada
| | - Emma Allen-Vercoe
- Department of Molecular and Cellular Biology, University of Guelph, Guelph, ON, Canada
| | - Erika C Claud
- Departments of Pediatrics and Medicine, The University of Chicago, Chicago, IL, United States
| | - Prameet M Sheth
- Gastrointestinal Disease Research Unit, Kingston Health Sciences Center, Kingston, ON, Canada; Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada; Division of Microbiology and Infectious Diseases, Kingston Health Sciences Center, Kingston, ON, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.
| | - Elaine O Petrof
- Gastrointestinal Disease Research Unit, Kingston Health Sciences Center, Kingston, ON, Canada; Division of Microbiology and Infectious Diseases, Kingston Health Sciences Center, Kingston, ON, Canada; Department of Medicine, Kingston Health Sciences Center, Kingston, ON, Canada
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Rebuilding the Gut Microbiota Ecosystem. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15081679. [PMID: 30087270 PMCID: PMC6121872 DOI: 10.3390/ijerph15081679] [Citation(s) in RCA: 193] [Impact Index Per Article: 27.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/19/2018] [Accepted: 08/04/2018] [Indexed: 11/17/2022]
Abstract
A microbial ecosystem in which bacteria no longer live in a mutualistic association is called dysbiotic. Gut microbiota dysbiosis is a condition related with the pathogenesis of intestinal illnesses (irritable bowel syndrome, celiac disease, and inflammatory bowel disease) and extra-intestinal illnesses (obesity, metabolic disorder, cardiovascular syndrome, allergy, and asthma). Dysbiosis status has been related to various important pathologies, and many therapeutic strategies aimed at restoring the balance of the intestinal ecosystem have been implemented. These strategies include the administration of probiotics, prebiotics, and synbiotics; phage therapy; fecal transplantation; bacterial consortium transplantation; and a still poorly investigated approach based on predatory bacteria. This review discusses the various aspects of these strategies to counteract intestinal dysbiosis.
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Shiraishi T, Yokota S, Sato Y, Ito T, Fukiya S, Yamamoto S, Sato T, Yokota A. Lipoteichoic acids are embedded in cell walls during logarithmic phase, but exposed on membrane vesicles in Lactobacillus gasseri JCM 1131 T. Benef Microbes 2018; 9:653-662. [PMID: 29633638 DOI: 10.3920/bm2017.0124] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Lipoteichoic acid (LTA) is a cell surface molecule specific to Gram-positive bacteria. How LTA localises on the cell surface is a fundamental issue in view of recognition and immunomodulation in hosts. In the present study, we examined LTA localisation using strain JCM 1131T of Lactobacillus gasseri, which is a human intestinal lactic acid bacterium, during various growth phases by immunoelectron microscopy. We first evaluated the specificity of anti-LTA monoclonal antibody clone 55 used as a probe. The glycerophosphate backbone comprising almost intact size (20 to 30 repeating units) of LTA was required for binding. The antibody did not bind to other cellular components, including wall-teichoic acid. Immunoelectron microscopy indicated that LTA was embedded in the cell wall during the logarithmic phase, and was therefore not exposed on the cell surface. Similar results were observed for Lactobacillus fermentum ATCC 9338 and Lactobacillus rhamnosus ATCC 7469T. By contrast, membrane vesicles were observed in the logarithmic phase of L. gasseri with LTA exposed on their surface. In the stationary and death phases, LTA was exposed on cell wall-free cell membrane generated by autolysis. The dramatic alternation of localisation in different growth phases and exposure on the surface of membrane vesicles should relate with complicated interaction between bacteria and host.
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Affiliation(s)
- T Shiraishi
- 1 Department of Microbiology, Sapporo Medical University School of Medicine, Minami 1 Nishi 17, Chuo-ku, Sapporo, Hokkaido 060-8556, Japan
| | - S Yokota
- 1 Department of Microbiology, Sapporo Medical University School of Medicine, Minami 1 Nishi 17, Chuo-ku, Sapporo, Hokkaido 060-8556, Japan
| | - Y Sato
- 2 Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan
| | - T Ito
- 3 Electron Microscope Laboratory, Research Faculty of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan
| | - S Fukiya
- 2 Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan
| | - S Yamamoto
- 1 Department of Microbiology, Sapporo Medical University School of Medicine, Minami 1 Nishi 17, Chuo-ku, Sapporo, Hokkaido 060-8556, Japan
| | - T Sato
- 1 Department of Microbiology, Sapporo Medical University School of Medicine, Minami 1 Nishi 17, Chuo-ku, Sapporo, Hokkaido 060-8556, Japan
| | - A Yokota
- 2 Laboratory of Microbial Physiology, Research Faculty of Agriculture, Hokkaido University, Kita 9 Nishi 9, Kita-ku, Sapporo, Hokkaido 060-8589, Japan
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Kurtz C, Denney WS, Blankstein L, Guilmain SE, Machinani S, Kotula J, Saha S, Miller P, Brennan AM. Translational Development of Microbiome-Based Therapeutics: Kinetics of E. coli Nissle and Engineered Strains in Humans and Nonhuman Primates. Clin Transl Sci 2018; 11:200-207. [PMID: 29194983 PMCID: PMC5866967 DOI: 10.1111/cts.12528] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Accepted: 11/09/2017] [Indexed: 12/12/2022] Open
Abstract
Understanding the pharmacology of microbiome-based therapeutics is required to support the development of new medicines. Strains of E. coli Nissle (EcN) were genetically modified and administered to cynomolgus monkeys at doses of 1 × 109 and 1 × 1012 colony-forming units (CFU)/day for 28 days. A clinical study to evaluate the exposure and clearance of EcN in healthy volunteers was also performed. Healthy subjects received oral doses of EcN, 2.5 to 25 × 109 CFU 3 times daily for 28 days or a single day. In cynomolgus monkeys, replicating strains yielded higher fecal concentrations than nonreplicating strains and persisted for longer following cessation of dosing. In the clinical study, all subjects cleared EcN following cessation of dosing with median clearance of 1 week. Quantitative methodology can be applied to microbiome-based therapeutics, and similar kinetics and clearance were observed for EcN in cynomolgus monkeys and humans.
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